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Wikipedia

Myc

April 15, 2024

For other uses, see MYC (disambiguation).

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors. The Myc family consists of three related human genes: c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). c-myc (also sometimes referred to as MYC) was the first gene to be discovered in this family, due to homology with the viral gene v-myc.

MYC proto-oncogene, bHLH transcription factor
Identifiers
SymbolMYC
Alt. symbolsc-Myc, v-myc
NCBI gene4609
HGNC7553
OMIM190080
RefSeqNM_001354870.1
UniProtP01106
Other data
LocusChr. 8 q24.21
WikidataQ20969939
Search for
StructuresSwiss-model
DomainsInterPro
MYCL proto-oncogene, bHLH transcription factor
Identifiers
SymbolMYCL
Alt. symbolsLMYC, MYCL1, bHLHe38, L-Myc, v-myc
NCBI gene4610
HGNC7555
OMIM164850
RefSeqNM_005376
UniProtP12524
Other data
LocusChr. 1 p34.2
WikidataQ18029714
Search for
StructuresSwiss-model
DomainsInterPro
MYCN proto-oncogene, bHLH transcription factor
Identifiers
SymbolMYCN
NCBI gene4613
HGNC7559
OMIM164840
RefSeqNM_005378
UniProtV
Other data
LocusChr. 2 p24.3
WikidataQ14906753
Search for
StructuresSwiss-model
DomainsInterPro

In cancer, c-myc is often constitutively (persistently) expressed. This leads to the increased expression of many genes, some of which are involved in cell proliferation, contributing to the formation of cancer.[1] A common human translocation involving c-myc is critical to the development of most cases of Burkitt lymphoma.[2] Constitutive upregulation of Myc genes have also been observed in carcinoma of the cervix, colon, breast, lung and stomach.[1]

Myc is thus viewed as a promising target for anti-cancer drugs.[3] Unfortunately, Myc possesses several features that have rendered it difficult to drug to date, such that any anti-cancer drugs aimed at inhibiting Myc may continue to require perturbing the protein indirectly, such as by targeting the mRNA for the protein rather than via a small molecule that targets the protein itself.[4][5]

c-Myc also plays an important role in stem cell biology and was one of the original Yamanaka factors used to reprogram somatic cells into induced pluripotent stem cells.[6]

In the human genome, C-myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes[7] through binding on enhancer box sequences (E-boxes).

In addition to its role as a classical transcription factor, N-myc may recruit histone acetyltransferases (HATs). This allows it to regulate global chromatin structure via histone acetylation.[8]

Discovery edit

The Myc family was first established after discovery of homology between an oncogene carried by the Avian virus, Myelocytomatosis (v-myc; P10395) and a human gene over-expressed in various cancers, cellular Myc (c-Myc).[citation needed] Later, discovery of further homologous genes in humans led to the addition of n-Myc and l-Myc to the family of genes.[9]

The most frequently discussed example of c-Myc as a proto-oncogene is its implication in Burkitt's lymphoma. In Burkitt's lymphoma, cancer cells show chromosomal translocations, most commonly between chromosome 8 and chromosome 14 [t(8;14)]. This causes c-Myc to be placed downstream of the highly active immunoglobulin (Ig) promoter region, leading to overexpression of Myc.

Structure edit

The protein product of Myc family genes all belong to the Myc family of transcription factors, which contain bHLH (basic helix-loop-helix) and LZ (leucine zipper) structural motifs. The bHLH motif allows Myc proteins to bind with DNA, while the leucine zipper TF-binding motif allows dimerization with Max, another bHLH transcription factor.

Myc mRNA contains an IRES (internal ribosome entry site) that allows the RNA to be translated into protein when 5' cap-dependent translation is inhibited, such as during viral infection.

Function edit

Myc proteins are transcription factors that activate expression of many pro-proliferative genes through binding enhancer box sequences (E-boxes) and recruiting histone acetyltransferases (HATs). Myc is thought to function by upregulating transcript elongation of actively transcribed genes through the recruitment of transcriptional elongation factors.[10] It can also act as a transcriptional repressor. By binding Miz-1 transcription factor and displacing the p300 co-activator, it inhibits expression of Miz-1 target genes. In addition, myc has a direct role in the control of DNA replication.[11] This activity could contribute to DNA amplification in cancer cells.[12]

Myc is activated upon various mitogenic signals such as serum stimulation or by Wnt, Shh and EGF (via the MAPK/ERK pathway).[13] By modifying the expression of its target genes, Myc activation results in numerous biological effects. The first to be discovered was its capability to drive cell proliferation (upregulates cyclins, downregulates p21), but it also plays a very important role in regulating cell growth (upregulates ribosomal RNA and proteins), apoptosis (downregulates Bcl-2), differentiation, and stem cell self-renewal. Nucleotide metabolism genes are upregulated by Myc,[14] which are necessary for Myc induced proliferation[15] or cell growth.[16]

There have been several studies that have clearly indicated Myc's role in cell competition.[17]

A major effect of c-myc is B cell proliferation, and gain of MYC has been associated with B cell malignancies and their increased aggressiveness, including histological transformation.[18] In B cells, Myc acts as a classical oncogene by regulating a number of pro-proliferative and anti-apoptotic pathways, this also includes tuning of BCR signaling and CD40 signaling in regulation of microRNAs (miR-29, miR-150, miR-17-92).[19]

c-Myc induces MTDH(AEG-1) gene expression and in turn itself requires AEG-1 oncogene for its expression.

Myc-nick edit

 
Myc-Nick

Myc-nick is a cytoplasmic form of Myc produced by a partial proteolytic cleavage of full-length c-Myc and N-Myc.[20] Myc cleavage is mediated by the calpain family of calcium-dependent cytosolic proteases.

The cleavage of Myc by calpains is a constitutive process but is enhanced under conditions that require rapid downregulation of Myc levels, such as during terminal differentiation. Upon cleavage, the C-terminus of Myc (containing the DNA binding domain) is degraded, while Myc-nick, the N-terminal segment 298-residue segment remains in the cytoplasm. Myc-nick contains binding domains for histone acetyltransferases and for ubiquitin ligases.

The functions of Myc-nick are currently under investigation, but this new Myc family member was found to regulate cell morphology, at least in part, by interacting with acetyl transferases to promote the acetylation of α-tubulin. Ectopic expression of Myc-nick accelerates the differentiation of committed myoblasts into muscle cells.

Clinical significance edit

A large body of evidence shows that Myc genes and proteins are highly relevant for treating tumors.[9] Except for early response genes, Myc universally upregulates gene expression. Furthermore, the upregulation is nonlinear. Genes for which expression is already significantly upregulated in the absence of Myc are strongly boosted in the presence of Myc, whereas genes for which expression is low in the absence Myc get only a small boost when Myc is present.[6]

Inactivation of SUMO-activating enzyme (SAE1 / SAE2) in the presence of Myc hyperactivation results in mitotic catastrophe and cell death in cancer cells. Hence inhibitors of SUMOylation may be a possible treatment for cancer.[21]

Amplification of the MYC gene was found in a significant number of epithelial ovarian cancer cases.[22] In TCGA datasets, the amplification of Myc occurs in several cancer types, including breast, colorectal, pancreatic, gastric, and uterine cancers.[23]

In the experimental transformation process of normal cells into cancer cells, the MYC gene can cooperate with the RAS gene.[24][25]

Expression of Myc is highly dependent on BRD4 function in some cancers.[26][27] BET inhibitors have been used to successfully block Myc function in pre-clinical cancer models and are currently being evaluated in clinical trials.[28]

MYC expression is controlled by a wide variety of noncoding RNAs, including miRNA, lncRNA, and circRNA. Some of these RNAs have been shown to be specific for certain types of human tissues and tumors.[29] Changes in the expression of such RNAs can potentially be used to develop targeted tumor therapy.

Animal models edit

In Drosophila Myc is encoded by the diminutive locus, (which was known to geneticists prior to 1935).[30] Classical diminutive alleles resulted in a viable animal with small body size. Drosophila has subsequently been used to implicate Myc in cell competition,[31] endoreplication,[32] and cell growth.[33]

During the discovery of Myc gene, it was realized that chromosomes that reciprocally translocate to chromosome 8 contained immunoglobulin genes at the break-point. To study the mechanism of tumorigenesis in Burkitt lymphoma by mimicking expression pattern of Myc in these cancer cells, transgenic mouse models were developed. Myc gene placed under the control of IgM heavy chain enhancer in transgenic mice gives rise to mainly lymphomas. Later on, in order to study effects of Myc in other types of cancer, transgenic mice that overexpress Myc in different tissues (liver, breast) were also made. In all these mouse models overexpression of Myc causes tumorigenesis, illustrating the potency of Myc oncogene. In a study with mice, reduced expression of Myc was shown to induce longevity, with significantly extended median and maximum lifespans in both sexes and a reduced mortality rate across all ages, better health, cancer progression was slower, better metabolism and they had smaller bodies. Also, Less TOR, AKT, S6K and other changes in energy and metabolic pathways (such as AMPK, more oxygen consumption, more body movements, etc.). The study by John M. Sedivy and others used Cre-Loxp -recombinase to knockout one copy of Myc and this resulted in a "Haplo-insufficient" genotype noted as Myc+/-. The phenotypes seen oppose the effects of normal aging and are shared with many other long-lived mouse models such as CR (calorie restriction) ames dwarf, rapamycin, metformin and resveratrol. One study found that Myc and p53 genes were key to the survival of chronic myeloid leukaemia (CML) cells. Targeting Myc and p53 proteins with drugs gave positive results on mice with CML.[34][35]

Relationship to stem cells edit

Myc genes play a number of normal roles in stem cells including pluripotent stem cells. In neural stem cells, N-Myc promotes a rapidly proliferative stem cell and precursor-like state in the developing brain, while inhibiting differentiation.[36] In hematopoietic stem cells, Myc controls the balance between self-renewal and differentiation.[37] In particular, long-term hematopoietic stem cells (LT-HSCs) express low levels of c-Myc, ensuring self-renewal. Enforced expression of c-Myc in LT-HSCs promotes differentiation at the expense of self-renewal, resulting in stem cell exhaustion.[38] In pathological states and specifically in acute myeloid leukemia, oxidant stress can trigger higher levels of Myc expression that affects the behavior of leukemia stem cells.[39]

c-Myc plays a major role in the generation of induced pluripotent stem cells (iPSCs). It is one of the original factors discovered by Yamanaka et al. to encourage cells to return to a 'stem-like' state alongside transcription factors Oct4, Sox2 and Klf4. It has since been shown that it is possible to generate iPSCs without c-Myc.[40]

Interactions edit

Myc has been shown to interact with:

 
Overview of signal transduction pathways involved in apoptosis.

See also edit

References edit

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Further reading edit

  • Ruf IK, Rhyne PW, Yang H, Borza CM, Hutt-Fletcher LM, Cleveland JL, Sample JT (2001). "EBV Regulates c-MYC, Apoptosis, and Tumorigenicity in Burkitt's Lymphoma". Epstein-Barr Virus and Human Cancer. Current Topics in Microbiology and Immunology. Vol. 258. pp. 153–60. doi:10.1007/978-3-642-56515-1_10. ISBN 978-3-642-62568-8. PMID 11443860.
  • Lüscher B (October 2001). "Function and regulation of the transcription factors of the Myc/Max/Mad network". Gene. 277 (1–2): 1–14. doi:10.1016/S0378-1119(01)00697-7. PMID 11602341.
  • Hoffman B, Amanullah A, Shafarenko M, Liebermann DA (May 2002). "The proto-oncogene c-myc in hematopoietic development and leukemogenesis". Oncogene. 21 (21): 3414–21. doi:10.1038/sj.onc.1205400. PMID 12032779. S2CID 8720539.
  • Pelengaris S, Khan M, Evan G (October 2002). "c-MYC: more than just a matter of life and death". Nature Reviews. Cancer. 2 (10): 764–76. doi:10.1038/nrc904. PMID 12360279. S2CID 13226062.
  • Nilsson JA, Cleveland JL (December 2003). "Myc pathways provoking cell suicide and cancer". Oncogene. 22 (56): 9007–21. doi:10.1038/sj.onc.1207261. PMID 14663479. S2CID 24758874.
  • Dang CV, O'donnell KA, Juopperi T (September 2005). "The great MYC escape in tumorigenesis". Cancer Cell. 8 (3): 177–8. doi:10.1016/j.ccr.2005.08.005. PMID 16169462.
  • Dang CV, Li F, Lee LA (November 2005). "Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability?". Cell Cycle. 4 (11): 1465–6. doi:10.4161/cc.4.11.2121. PMID 16205115.
  • Coller HA, Forman JJ, Legesse-Miller A (August 2007). ""Myc'ed messages": myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron". PLOS Genetics. 3 (8): e146. doi:10.1371/journal.pgen.0030146. PMC 1959363. PMID 17784791.
  • Astrin SM, Laurence J (May 1992). "Human immunodeficiency virus activates c-myc and Epstein-Barr virus in human B lymphocytes". Annals of the New York Academy of Sciences. 651 (1): 422–32. Bibcode:1992NYASA.651..422A. doi:10.1111/j.1749-6632.1992.tb24642.x. PMID 1318011. S2CID 31980333.
  • Bernstein PL, Herrick DJ, Prokipcak RD, Ross J (April 1992). "Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant". Genes & Development. 6 (4): 642–54. doi:10.1101/gad.6.4.642. PMID 1559612.
  • Iijima S, Teraoka H, Date T, Tsukada K (June 1992). "DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein". European Journal of Biochemistry. 206 (2): 595–603. doi:10.1111/j.1432-1033.1992.tb16964.x. PMID 1597196.
  • Seth A, Alvarez E, Gupta S, Davis RJ (December 1991). "A phosphorylation site located in the NH2-terminal domain of c-Myc increases transactivation of gene expression". The Journal of Biological Chemistry. 266 (35): 23521–4. doi:10.1016/S0021-9258(18)54312-X. PMID 1748630.
  • Takahashi E, Hori T, O'Connell P, Leppert M, White R (1991). "Mapping of the MYC gene to band 8q24.12----q24.13 by R-banding and distal to fra(8)(q24.11), FRA8E, by fluorescence in situ hybridization". Cytogenetics and Cell Genetics. 57 (2–3): 109–11. doi:10.1159/000133124. PMID 1914517.
  • Blackwood EM, Eisenman RN (March 1991). "Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc". Science. 251 (4998): 1211–7. Bibcode:1991Sci...251.1211B. doi:10.1126/science.2006410. PMID 2006410.
  • Gazin C, Rigolet M, Briand JP, Van Regenmortel MH, Galibert F (September 1986). "Immunochemical detection of proteins related to the human c-myc exon 1". The EMBO Journal. 5 (9): 2241–50. doi:10.1002/j.1460-2075.1986.tb04491.x. PMC 1167107. PMID 2430795.
  • Lüscher B, Kuenzel EA, Krebs EG, Eisenman RN (April 1989). "Myc oncoproteins are phosphorylated by casein kinase II". The EMBO Journal. 8 (4): 1111–9. doi:10.1002/j.1460-2075.1989.tb03481.x. PMC 400922. PMID 2663470.
  • Finver SN, Nishikura K, Finger LR, Haluska FG, Finan J, Nowell PC, Croce CM (May 1988). "Sequence analysis of the MYC oncogene involved in the t(8;14)(q24;q11) chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered". Proceedings of the National Academy of Sciences of the United States of America. 85 (9): 3052–6. Bibcode:1988PNAS...85.3052F. doi:10.1073/pnas.85.9.3052. PMC 280141. PMID 2834731.
  • Showe LC, Moore RC, Erikson J, Croce CM (May 1987). "MYC oncogene involved in a t(8;22) chromosome translocation is not altered in its putative regulatory regions". Proceedings of the National Academy of Sciences of the United States of America. 84 (9): 2824–8. Bibcode:1987PNAS...84.2824S. doi:10.1073/pnas.84.9.2824. PMC 304752. PMID 3033665.
  • Guilhot S, Petridou B, Syed-Hussain S, Galibert F (December 1988). "Nucleotide sequence 3' to the human c-myc oncogene; presence of a long inverted repeat". Gene. 72 (1–2): 105–8. doi:10.1016/0378-1119(88)90131-X. PMID 3243428.
  • Hann SR, King MW, Bentley DL, Anderson CW, Eisenman RN (January 1988). "A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas". Cell. 52 (2): 185–95. doi:10.1016/0092-8674(88)90507-7. PMID 3277717. S2CID 3012009.

External links edit

  • InterPro signatures for protein family: IPR002418, IPR011598, IPR003327
  • The Myc Protein
  • NCBI Human Myc protein
  • Myc cancer gene
  • myc+Proto-Oncogene+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  • Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4
  • Drosophila Myc - The Interactive Fly
  • FactorBook C-Myc
  • PDBe-KB provides an overview of all the structure information available in the PDB for Human Myc proto-oncogene protein

April 15, 2024
other, uses, disambiguation, family, regulator, genes, proto, oncogenes, that, code, transcription, factors, family, consists, three, related, human, genes, mycl, mycn, also, sometimes, referred, first, gene, discovered, this, family, homology, with, viral, ge. For other uses see MYC disambiguation Myc is a family of regulator genes and proto oncogenes that code for transcription factors The Myc family consists of three related human genes c myc MYC l myc MYCL and n myc MYCN c myc also sometimes referred to as MYC was the first gene to be discovered in this family due to homology with the viral gene v myc MYC proto oncogene bHLH transcription factorIdentifiersSymbolMYCAlt symbolsc Myc v mycNCBI gene4609HGNC7553OMIM190080RefSeqNM 001354870 1UniProtP01106Other dataLocusChr 8 q24 21WikidataQ20969939Search forStructuresSwiss modelDomainsInterProMYCL proto oncogene bHLH transcription factorIdentifiersSymbolMYCLAlt symbolsLMYC MYCL1 bHLHe38 L Myc v mycNCBI gene4610HGNC7555OMIM164850RefSeqNM 005376UniProtP12524Other dataLocusChr 1 p34 2WikidataQ18029714Search forStructuresSwiss modelDomainsInterProMYCN proto oncogene bHLH transcription factorIdentifiersSymbolMYCNNCBI gene4613HGNC7559OMIM164840RefSeqNM 005378UniProtVOther dataLocusChr 2 p24 3WikidataQ14906753Search forStructuresSwiss modelDomainsInterProIn cancer c myc is often constitutively persistently expressed This leads to the increased expression of many genes some of which are involved in cell proliferation contributing to the formation of cancer 1 A common human translocation involving c myc is critical to the development of most cases of Burkitt lymphoma 2 Constitutive upregulation of Myc genes have also been observed in carcinoma of the cervix colon breast lung and stomach 1 Myc is thus viewed as a promising target for anti cancer drugs 3 Unfortunately Myc possesses several features that have rendered it difficult to drug to date such that any anti cancer drugs aimed at inhibiting Myc may continue to require perturbing the protein indirectly such as by targeting the mRNA for the protein rather than via a small molecule that targets the protein itself 4 5 c Myc also plays an important role in stem cell biology and was one of the original Yamanaka factors used to reprogram somatic cells into induced pluripotent stem cells 6 In the human genome C myc is located on chromosome 8 and is believed to regulate expression of 15 of all genes 7 through binding on enhancer box sequences E boxes In addition to its role as a classical transcription factor N myc may recruit histone acetyltransferases HATs This allows it to regulate global chromatin structure via histone acetylation 8 Contents 1 Discovery 2 Structure 3 Function 4 Myc nick 5 Clinical significance 6 Animal models 7 Relationship to stem cells 8 Interactions 9 See also 10 References 11 Further reading 12 External linksDiscovery editThe Myc family was first established after discovery of homology between an oncogene carried by the Avian virus Myelocytomatosis v myc P10395 and a human gene over expressed in various cancers cellular Myc c Myc citation needed Later discovery of further homologous genes in humans led to the addition of n Myc and l Myc to the family of genes 9 The most frequently discussed example of c Myc as a proto oncogene is its implication in Burkitt s lymphoma In Burkitt s lymphoma cancer cells show chromosomal translocations most commonly between chromosome 8 and chromosome 14 t 8 14 This causes c Myc to be placed downstream of the highly active immunoglobulin Ig promoter region leading to overexpression of Myc Structure editThe protein product of Myc family genes all belong to the Myc family of transcription factors which contain bHLH basic helix loop helix and LZ leucine zipper structural motifs The bHLH motif allows Myc proteins to bind with DNA while the leucine zipper TF binding motif allows dimerization with Max another bHLH transcription factor Myc mRNA contains an IRES internal ribosome entry site that allows the RNA to be translated into protein when 5 cap dependent translation is inhibited such as during viral infection Function editMyc proteins are transcription factors that activate expression of many pro proliferative genes through binding enhancer box sequences E boxes and recruiting histone acetyltransferases HATs Myc is thought to function by upregulating transcript elongation of actively transcribed genes through the recruitment of transcriptional elongation factors 10 It can also act as a transcriptional repressor By binding Miz 1 transcription factor and displacing the p300 co activator it inhibits expression of Miz 1 target genes In addition myc has a direct role in the control of DNA replication 11 This activity could contribute to DNA amplification in cancer cells 12 Myc is activated upon various mitogenic signals such as serum stimulation or by Wnt Shh and EGF via the MAPK ERK pathway 13 By modifying the expression of its target genes Myc activation results in numerous biological effects The first to be discovered was its capability to drive cell proliferation upregulates cyclins downregulates p21 but it also plays a very important role in regulating cell growth upregulates ribosomal RNA and proteins apoptosis downregulates Bcl 2 differentiation and stem cell self renewal Nucleotide metabolism genes are upregulated by Myc 14 which are necessary for Myc induced proliferation 15 or cell growth 16 There have been several studies that have clearly indicated Myc s role in cell competition 17 A major effect of c myc is B cell proliferation and gain of MYC has been associated with B cell malignancies and their increased aggressiveness including histological transformation 18 In B cells Myc acts as a classical oncogene by regulating a number of pro proliferative and anti apoptotic pathways this also includes tuning of BCR signaling and CD40 signaling in regulation of microRNAs miR 29 miR 150 miR 17 92 19 c Myc induces MTDH AEG 1 gene expression and in turn itself requires AEG 1 oncogene for its expression Myc nick edit nbsp Myc NickMyc nick is a cytoplasmic form of Myc produced by a partial proteolytic cleavage of full length c Myc and N Myc 20 Myc cleavage is mediated by the calpain family of calcium dependent cytosolic proteases The cleavage of Myc by calpains is a constitutive process but is enhanced under conditions that require rapid downregulation of Myc levels such as during terminal differentiation Upon cleavage the C terminus of Myc containing the DNA binding domain is degraded while Myc nick the N terminal segment 298 residue segment remains in the cytoplasm Myc nick contains binding domains for histone acetyltransferases and for ubiquitin ligases The functions of Myc nick are currently under investigation but this new Myc family member was found to regulate cell morphology at least in part by interacting with acetyl transferases to promote the acetylation of a tubulin Ectopic expression of Myc nick accelerates the differentiation of committed myoblasts into muscle cells Clinical significance editA large body of evidence shows that Myc genes and proteins are highly relevant for treating tumors 9 Except for early response genes Myc universally upregulates gene expression Furthermore the upregulation is nonlinear Genes for which expression is already significantly upregulated in the absence of Myc are strongly boosted in the presence of Myc whereas genes for which expression is low in the absence Myc get only a small boost when Myc is present 6 Inactivation of SUMO activating enzyme SAE1 SAE2 in the presence of Myc hyperactivation results in mitotic catastrophe and cell death in cancer cells Hence inhibitors of SUMOylation may be a possible treatment for cancer 21 Amplification of the MYC gene was found in a significant number of epithelial ovarian cancer cases 22 In TCGA datasets the amplification of Myc occurs in several cancer types including breast colorectal pancreatic gastric and uterine cancers 23 In the experimental transformation process of normal cells into cancer cells the MYC gene can cooperate with the RAS gene 24 25 Expression of Myc is highly dependent on BRD4 function in some cancers 26 27 BET inhibitors have been used to successfully block Myc function in pre clinical cancer models and are currently being evaluated in clinical trials 28 MYC expression is controlled by a wide variety of noncoding RNAs including miRNA lncRNA and circRNA Some of these RNAs have been shown to be specific for certain types of human tissues and tumors 29 Changes in the expression of such RNAs can potentially be used to develop targeted tumor therapy Animal models editIn Drosophila Myc is encoded by the diminutive locus which was known to geneticists prior to 1935 30 Classical diminutive alleles resulted in a viable animal with small body size Drosophila has subsequently been used to implicate Myc in cell competition 31 endoreplication 32 and cell growth 33 During the discovery of Myc gene it was realized that chromosomes that reciprocally translocate to chromosome 8 contained immunoglobulin genes at the break point To study the mechanism of tumorigenesis in Burkitt lymphoma by mimicking expression pattern of Myc in these cancer cells transgenic mouse models were developed Myc gene placed under the control of IgM heavy chain enhancer in transgenic mice gives rise to mainly lymphomas Later on in order to study effects of Myc in other types of cancer transgenic mice that overexpress Myc in different tissues liver breast were also made In all these mouse models overexpression of Myc causes tumorigenesis illustrating the potency of Myc oncogene In a study with mice reduced expression of Myc was shown to induce longevity with significantly extended median and maximum lifespans in both sexes and a reduced mortality rate across all ages better health cancer progression was slower better metabolism and they had smaller bodies Also Less TOR AKT S6K and other changes in energy and metabolic pathways such as AMPK more oxygen consumption more body movements etc The study by John M Sedivy and others used Cre Loxp recombinase to knockout one copy of Myc and this resulted in a Haplo insufficient genotype noted as Myc The phenotypes seen oppose the effects of normal aging and are shared with many other long lived mouse models such as CR calorie restriction ames dwarf rapamycin metformin and resveratrol One study found that Myc and p53 genes were key to the survival of chronic myeloid leukaemia CML cells Targeting Myc and p53 proteins with drugs gave positive results on mice with CML 34 35 Relationship to stem cells editMyc genes play a number of normal roles in stem cells including pluripotent stem cells In neural stem cells N Myc promotes a rapidly proliferative stem cell and precursor like state in the developing brain while inhibiting differentiation 36 In hematopoietic stem cells Myc controls the balance between self renewal and differentiation 37 In particular long term hematopoietic stem cells LT HSCs express low levels of c Myc ensuring self renewal Enforced expression of c Myc in LT HSCs promotes differentiation at the expense of self renewal resulting in stem cell exhaustion 38 In pathological states and specifically in acute myeloid leukemia oxidant stress can trigger higher levels of Myc expression that affects the behavior of leukemia stem cells 39 c Myc plays a major role in the generation of induced pluripotent stem cells iPSCs It is one of the original factors discovered by Yamanaka et al to encourage cells to return to a stem like state alongside transcription factors Oct4 Sox2 and Klf4 It has since been shown that it is possible to generate iPSCs without c Myc 40 Interactions editMyc has been shown to interact with ACTL6A 41 BRCA1 42 43 44 45 Bcl 2 46 Cyclin T1 47 CHD8 48 DNMT3A 49 EP400 50 GTF2I 51 HTATIP 52 let 7 53 54 55 MAPK1 46 56 57 MAPK8 58 MAX 59 60 61 62 63 64 65 66 67 68 69 70 71 MLH1 63 MYCBP2 72 MYCBP 73 NMI 42 NFYB 74 NFYC 75 P73 76 PCAF 77 PFDN5 78 79 RuvB like 1 41 50 SAP130 77 SMAD2 80 SMAD3 80 SMARCA4 41 59 SMARCB1 62 SUPT3H 77 TIAM1 81 TADA2L 77 TAF9 77 TFAP2A 82 TRRAP 41 60 61 77 WDR5 83 YY1 84 and ZBTB17 85 86 C2orf16 87 nbsp Overview of signal transduction pathways involved in apoptosis See also editMyc tag C myc mRNAReferences edit a b Myc NCBI Finver SN Nishikura K Finger LR Haluska FG Finan J Nowell PC Croce CM May 1988 Sequence analysis of the Myc oncogene involved in the t 8 14 q24 q11 chromosome translocation in a human leukemia T cell line indicates that putative regulatory regions are not altered Proceedings of the National Academy of Sciences of the United States of America 85 9 3052 6 Bibcode 1988PNAS 85 3052F doi 10 1073 pnas 85 9 3052 PMC 280141 PMID 2834731 Begley S 2013 01 09 DNA pioneer James Watson takes aim at cancer establishments Reuters Carabet LA Rennie PS Cherkasov A December 2018 Therapeutic Inhibition of Myc in Cancer Structural Bases and Computer Aided Drug Discovery Approaches International Journal of Molecular Sciences 20 1 120 doi 10 3390 ijms20010120 PMC 6337544 PMID 30597997 Dang CV Reddy EP Shokat KM Soucek L August 2017 Drugging the undruggable cancer targets Nature Reviews Cancer 17 8 502 508 doi 10 1038 nrc 2017 36 PMC 5945194 PMID 28643779 a b Nie Z Hu G Wei G Cui K Yamane A Resch W Wang R Green DR Tessarollo L Casellas R Zhao K Levens D September 2012 c Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells Cell 151 1 68 79 doi 10 1016 j cell 2012 08 033 PMC 3471363 PMID 23021216 Gearhart J Pashos EE Prasad MK October 2007 Pluripotency redux advances in stem cell research The New England Journal of Medicine 357 15 1469 72 doi 10 1056 NEJMp078126 PMID 17928593 Cotterman R Jin VX Krig SR Lemen JM Wey A Farnham PJ Knoepfler PS December 2008 N Myc regulates a widespread euchromatic program in the human genome partially independent of its role as a classical transcription factor Cancer Research 68 23 9654 62 doi 10 1158 0008 5472 CAN 08 1961 PMC 2637654 PMID 19047142 a b Wolf E Eilers M 2020 Targeting MYC Proteins for Tumor Therapy Annual Review of Cancer Biology 4 61 75 doi 10 1146 annurev cancerbio 030518 055826 Rahl PB Young RA January 2014 MYC and transcription elongation Cold Spring Harbor Perspectives in Medicine 4 1 a020990 doi 10 1101 cshperspect a020990 PMC 3869279 PMID 24384817 Dominguez Sola D Ying CY Grandori C Ruggiero L Chen B Li M Galloway DA Gu W Gautier J Dalla Favera R July 2007 Non transcriptional control of DNA replication by c Myc Nature 448 7152 445 51 Bibcode 2007Natur 448 445D doi 10 1038 nature05953 PMID 17597761 S2CID 4422771 Denis N Kitzis A Kruh J Dautry F Corcos D August 1991 Stimulation of methotrexate resistance and dihydrofolate reductase gene amplification by c myc Oncogene 6 8 1453 7 PMID 1886715 Campisi J Gray HE Pardee AB Dean M Sonenshein GE 1984 Cell cycle control of c myc but not c ras expression is lost following chemical transformation Cell 36 2 241 7 doi 10 1016 0092 8674 84 90217 4 PMID 6692471 S2CID 29661004 Liu YC Li F Handler J Huang CR Xiang Y Neretti N Sedivy JM Zeller KI Dang CV July 2008 Global regulation of nucleotide biosynthetic genes by c Myc PLOS ONE 3 7 e2722 Bibcode 2008PLoSO 3 2722L doi 10 1371 journal pone 0002722 PMC 2444028 PMID 18628958 Mannava S Grachtchouk V Wheeler LJ Im M Zhuang D Slavina EG Mathews CK Shewach DS Nikiforov MA August 2008 Direct role of nucleotide metabolism in C MYC dependent proliferation of melanoma cells Cell Cycle 7 15 2392 400 doi 10 4161 cc 6390 PMC 3744895 PMID 18677108 Aughey GN Grice SJ Liu JL February 2016 The Interplay between Myc and CTP Synthase in Drosophila PLOS Genetics 12 2 e1005867 doi 10 1371 journal pgen 1005867 PMC 4759343 PMID 26889675 Claveria C Giovinazzo G Sierra R Torres M August 2013 Myc driven endogenous cell competition in the early mammalian embryo Nature 500 7460 39 44 Bibcode 2013Natur 500 39C doi 10 1038 nature12389 PMID 23842495 S2CID 4414411 de Alboran IM O Hagan RC Gartner F Malynn B Davidson L Rickert R Rajewsky K DePinho RA Alt FW January 2001 Analysis of C MYC function in normal cells via conditional gene targeted mutation Immunity 14 1 45 55 doi 10 1016 S1074 7613 01 00088 7 PMID 11163229 Mendell JT April 2008 miRiad roles for the miR 17 92 cluster in development and disease Cell 133 2 217 22 doi 10 1016 j cell 2008 04 001 PMC 2732113 PMID 18423194 Conacci Sorrell M Ngouenet C Eisenman RN August 2010 Myc nick a cytoplasmic cleavage product of Myc that promotes alpha tubulin acetylation and cell differentiation Cell 142 3 480 93 doi 10 1016 j cell 2010 06 037 PMC 2923036 PMID 20691906 Kessler JD Kahle KT Sun T Meerbrey KL Schlabach MR Schmitt EM Skinner SO Xu Q Li MZ Hartman ZC Rao M Yu P Dominguez Vidana R Liang AC Solimini NL Bernardi RJ Yu B Hsu T Golding I Luo J Osborne CK Creighton CJ Hilsenbeck SG Schiff R Shaw CA Elledge SJ Westbrook TF January 2012 A SUMOylation dependent transcriptional subprogram is required for Myc driven tumorigenesis Science 335 6066 348 53 Bibcode 2012Sci 335 348K doi 10 1126 science 1212728 PMC 4059214 PMID 22157079 Ross JS Ali SM Wang K Palmer G Yelensky R Lipson D Miller VA Zajchowski D Shawver LK Stephens PJ 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retroviral dose Acta Neuropathologica 86 5 456 65 doi 10 1007 bf00228580 PMID 8310796 S2CID 2972931 Fowler T Ghatak P Price DH Conaway R Conaway J Chiang CM Bradner JE Shilatifard A Roy AL 2014 Regulation of MYC expression and differential JQ1 sensitivity in cancer cells PLOS ONE 9 1 e87003 Bibcode 2014PLoSO 987003F doi 10 1371 journal pone 0087003 PMC 3900694 PMID 24466310 Shi J Vakoc CR June 2014 The mechanisms behind the therapeutic activity of BET bromodomain inhibition Molecular Cell 54 5 728 36 doi 10 1016 j molcel 2014 05 016 PMC 4236231 PMID 24905006 Delmore JE Issa GC Lemieux ME Rahl PB Shi J Jacobs HM Kastritis E Gilpatrick T Paranal RM Qi J Chesi M Schinzel AC McKeown MR Heffernan TP Vakoc CR Bergsagel PL Ghobrial IM Richardson PG Young RA Hahn WC Anderson KC Kung AL Bradner JE Mitsiades CS September 2011 BET bromodomain inhibition as a therapeutic strategy to target c Myc Cell 146 6 904 17 doi 10 1016 j cell 2011 08 017 PMC 3187920 PMID 21889194 Stasevich EM Murashko MM Zinevich LS Demin DE Schwartz AM July 2021 The Role of Non Coding RNAs in the Regulation of the Proto Oncogene MYC in Different Types of Cancer Biomedicines 9 8 921 doi 10 3390 biomedicines9080921 PMC 8389562 PMID 34440124 Slizynska H May 1938 Salivary Chromosome Analysis of the White Facet Region of Drosophila Melanogaster Genetics 23 3 291 9 doi 10 1093 genetics 23 3 291 PMC 1209013 PMID 17246888 de la Cova C Abril M Bellosta P Gallant P Johnston LA April 2004 Drosophila myc regulates organ size by inducing cell competition Cell 117 1 107 16 doi 10 1016 S0092 8674 04 00214 4 PMID 15066286 S2CID 18357397 Maines JZ Stevens LM Tong X Stein D February 2004 Drosophila dMyc is required for ovary cell growth and endoreplication Development 131 4 775 86 doi 10 1242 dev 00932 PMID 14724122 S2CID 721144 Johnston LA Prober DA Edgar BA Eisenman RN Gallant P September 1999 Drosophila myc regulates cellular growth during development PDF Cell 98 6 779 90 doi 10 1016 S0092 8674 00 81512 3 PMC 10176494 PMID 10499795 S2CID 5215149 Archived from the original PDF on 2022 04 03 Retrieved 2020 03 20 Abraham SA Hopcroft LE Carrick E Drotar ME Dunn K Williamson AJ et al June 2016 Dual targeting of p53 and c MYC selectively eliminates leukaemic stem cells Nature 534 7607 341 6 Bibcode 2016Natur 534 341A doi 10 1038 nature18288 PMC 4913876 PMID 27281222 Scientists identify drugs to target Achilles heel of Chronic Myeloid Leukaemia cells myScience 2016 06 08 Archived from the original on 2018 07 27 Retrieved 2016 06 09 Knoepfler PS Cheng PF Eisenman RN October 2002 N myc is essential during neurogenesis for the rapid expansion of progenitor cell populations and the inhibition of neuronal differentiation Genes amp Development 16 20 2699 712 doi 10 1101 gad 1021202 PMC 187459 PMID 12381668 Wilson A Murphy MJ Oskarsson T Kaloulis K Bettess MD Oser GM et al November 2004 c Myc controls the balance between hematopoietic stem cell self renewal and differentiation Genes amp Development 18 22 2747 63 doi 10 1101 gad 313104 PMC 528895 PMID 15545632 Wilson A Murphy MJ Oskarsson T Kaloulis K Bettess MD Oser GM et al November 2004 c Myc controls the balance between hematopoietic stem cell self renewal and differentiation Genes amp Development 18 22 2747 63 doi 10 1101 gad 313104 PMC 528895 PMID 15545632 Vlahopoulos S Pan L Varisli L Dancik GM Karantanos T Boldogh I Dec 2023 OGG1 as an Epigenetic Reader Affects NFkB What This Means for Cancer Cancers Basel 16 1 148 doi 10 3390 cancers16010148 PMC 10778025 PMID 38201575 Takahashi K Yamanaka S March 2016 A decade of transcription factor mediated reprogramming to pluripotency Nature Reviews Molecular Cell Biology 17 3 183 93 doi 10 1038 nrm 2016 8 PMID 26883003 S2CID 7593915 a b c d Park J Wood MA Cole MD March 2002 BAF53 forms distinct nuclear complexes and functions as a critical c Myc interacting nuclear cofactor for oncogenic transformation Molecular and Cellular Biology 22 5 1307 16 doi 10 1128 mcb 22 5 1307 1316 2002 PMC 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sj onc 1202403 PMID 9788437 S2CID 30771256 a b Jin Z Gao F Flagg T Deng X September 2004 Tobacco specific nitrosamine 4 methylnitrosamino 1 3 pyridyl 1 butanone promotes functional cooperation of Bcl2 and c Myc through phosphorylation in regulating cell survival and proliferation The Journal of Biological Chemistry 279 38 40209 19 doi 10 1074 jbc M404056200 PMID 15210690 Kanazawa S Soucek L Evan G Okamoto T Peterlin BM August 2003 c Myc recruits P TEFb for transcription cellular proliferation and apoptosis Oncogene 22 36 5707 11 doi 10 1038 sj onc 1206800 PMID 12944920 S2CID 29519364 Dingar D Kalkat M Chan PK Srikumar T Bailey SD Tu WB Coyaud E Ponzielli R Kolyar M Jurisica I Huang A Lupien M Penn LZ Raught B April 2015 BioID identifies novel c MYC interacting partners in cultured cells and xenograft tumors Journal of Proteomics 118 12 95 111 doi 10 1016 j jprot 2014 09 029 PMID 25452129 Brenner C Deplus R Didelot C Loriot A Vire E De Smet C Gutierrez A Danovi D Bernard D Boon T Pelicci PG Amati B Kouzarides T de Launoit Y Di Croce L Fuks F January 2005 Myc represses transcription through recruitment of DNA methyltransferase corepressor The EMBO Journal 24 2 336 46 doi 10 1038 sj emboj 7600509 PMC 545804 PMID 15616584 a b Fuchs M Gerber J Drapkin R Sif S Ikura T Ogryzko V Lane WS Nakatani Y Livingston DM August 2001 The p400 complex is an essential E1A transformation target Cell 106 3 297 307 doi 10 1016 s0092 8674 01 00450 0 PMID 11509179 S2CID 15634637 Roy AL Carruthers C Gutjahr T Roeder RG September 1993 Direct role for Myc in transcription initiation mediated by interactions with TFII I Nature 365 6444 359 61 Bibcode 1993Natur 365 359R doi 10 1038 365359a0 PMID 8377829 S2CID 4354157 Frank SR Parisi T Taubert S Fernandez P Fuchs M Chan HM Livingston DM Amati B June 2003 MYC recruits the TIP60 histone acetyltransferase complex to chromatin EMBO Reports 4 6 575 80 doi 10 1038 sj embor embor861 PMC 1319201 PMID 12776177 Chang TC Yu D Lee YS Wentzel EA Arking DE West KM Dang CV Thomas Tikhonenko A Mendell JT January 2008 Widespread microRNA repression by Myc contributes to tumorigenesis Nature Genetics 40 1 43 50 doi 10 1038 ng 2007 30 PMC 2628762 PMID 18066065 Koscianska E Baev V Skreka K Oikonomaki K Rusinov V Tabler M Kalantidis K 2007 Prediction and preliminary validation of oncogene regulation by miRNAs BMC Molecular Biology 8 79 doi 10 1186 1471 2199 8 79 PMC 2096627 PMID 17877811 Ioannidis P Mahaira LG Perez SA Gritzapis AD Sotiropoulou PA Kavalakis GJ Antsaklis AI Baxevanis CN Papamichail M May 2005 CRD BP IMP1 expression characterizes cord blood CD34 stem cells and affects c myc and IGF II expression in MCF 7 cancer cells The Journal of Biological Chemistry 280 20 20086 93 doi 10 1074 jbc M410036200 PMID 15769738 Gupta S Davis RJ October 1994 MAP kinase binds to the NH2 terminal activation domain of c Myc FEBS Letters 353 3 281 5 doi 10 1016 0014 5793 94 01052 8 PMID 7957875 S2CID 45404088 Tournier C Whitmarsh AJ Cavanagh J Barrett T Davis RJ July 1997 Mitogen activated protein kinase kinase 7 is an activator of the c Jun NH2 terminal kinase Proceedings of the National Academy of Sciences of the United States of America 94 14 7337 42 Bibcode 1997PNAS 94 7337T doi 10 1073 pnas 94 14 7337 PMC 23822 PMID 9207092 Noguchi K Kitanaka C Yamana H Kokubu A Mochizuki T Kuchino Y November 1999 Regulation of c Myc through phosphorylation at Ser 62 and Ser 71 by c Jun N terminal kinase The Journal of Biological Chemistry 274 46 32580 7 doi 10 1074 jbc 274 46 32580 PMID 10551811 a b Ewing RM Chu P Elisma F Li H Taylor P Climie S McBroom Cerajewski L Robinson MD O Connor L Li M Taylor R Dharsee M Ho Y Heilbut A Moore L Zhang S Ornatsky O Bukhman YV Ethier M Sheng Y Vasilescu J Abu Farha M Lambert JP Duewel HS Stewart II Kuehl B Hogue K Colwill K Gladwish K Muskat B Kinach R Adams SL Moran MF Morin GB Topaloglou T Figeys D 2007 Large scale mapping of human protein protein interactions by mass spectrometry Molecular Systems Biology 3 89 doi 10 1038 msb4100134 PMC 1847948 PMID 17353931 a b McMahon SB Wood MA Cole MD January 2000 The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c Myc Molecular and Cellular Biology 20 2 556 62 doi 10 1128 mcb 20 2 556 562 2000 PMC 85131 PMID 10611234 a b McMahon SB Van Buskirk HA Dugan KA Copeland TD Cole MD August 1998 The novel ATM related protein TRRAP is an essential cofactor for the c Myc and E2F oncoproteins Cell 94 3 363 74 doi 10 1016 s0092 8674 00 81479 8 PMID 9708738 S2CID 17693834 a b Cheng SW Davies KP Yung E Beltran RJ Yu J Kalpana GV May 1999 c MYC interacts with INI1 hSNF5 and requires the SWI SNF complex for transactivation function Nature Genetics 22 1 102 5 doi 10 1038 8811 PMID 10319872 S2CID 12945791 a b Mac Partlin M Homer E Robinson H McCormick CJ Crouch DH Durant ST Matheson EC Hall AG Gillespie DA Brown R February 2003 Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c MYC and MAX Oncogene 22 6 819 25 doi 10 1038 sj onc 1206252 PMID 12584560 Blackwood EM Eisenman RN March 1991 Max a helix loop helix zipper protein that forms a sequence specific DNA binding complex with Myc Science 251 4998 1211 7 Bibcode 1991Sci 251 1211B doi 10 1126 science 2006410 PMID 2006410 Lee CM Onesime D Reddy CD Dhanasekaran N Reddy EP October 2002 JLP A scaffolding protein that tethers JNK p38MAPK signaling modules and transcription factors Proceedings of the National Academy of Sciences of the United States of America 99 22 14189 94 Bibcode 2002PNAS 9914189L doi 10 1073 pnas 232310199 PMC 137859 PMID 12391307 Billin AN Eilers AL Queva C Ayer DE December 1999 Mlx a novel Max like BHLHZip protein that interacts with the Max network of transcription factors The Journal of Biological Chemistry 274 51 36344 50 doi 10 1074 jbc 274 51 36344 PMID 10593926 Gupta K Anand G Yin X Grove L Prochownik EV March 1998 Mmip1 a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c myc Oncogene 16 9 1149 59 doi 10 1038 sj onc 1201634 PMID 9528857 S2CID 30576019 Meroni G Reymond A Alcalay M Borsani G Tanigami A Tonlorenzi R Lo Nigro C Messali S Zollo M Ledbetter DH Brent R Ballabio A Carrozzo R May 1997 Rox a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max binds a non canonical E box and acts as a transcriptional repressor The EMBO Journal 16 10 2892 906 doi 10 1093 emboj 16 10 2892 PMC 1169897 PMID 9184233 Nair SK Burley SK January 2003 X ray structures of Myc Max and Mad Max recognizing DNA Molecular bases of regulation by proto oncogenic transcription factors Cell 112 2 193 205 doi 10 1016 s0092 8674 02 01284 9 PMID 12553908 S2CID 16142388 FitzGerald MJ Arsura M Bellas RE Yang W Wu M Chin L Mann KK DePinho RA Sonenshein GE April 1999 Differential effects of the widely expressed dMax splice variant of Max on E box vs initiator element mediated regulation by c Myc Oncogene 18 15 2489 98 doi 10 1038 sj onc 1202611 PMID 10229200 Meroni G Cairo S Merla G Messali S Brent R Ballabio A Reymond A July 2000 Mlx a new Max like bHLHZip family member the center stage of a novel transcription factors regulatory pathway Oncogene 19 29 3266 77 doi 10 1038 sj onc 1203634 PMID 10918583 S2CID 17891130 Guo Q Xie J Dang CV Liu ET Bishop JM August 1998 Identification of a large Myc binding protein that contains RCC1 like repeats Proceedings of the National Academy of Sciences of the United States of America 95 16 9172 7 Bibcode 1998PNAS 95 9172G doi 10 1073 pnas 95 16 9172 PMC 21311 PMID 9689053 Taira T Maeda J Onishi T Kitaura H Yoshida S Kato H Ikeda M Tamai K Iguchi Ariga SM Ariga H August 1998 AMY 1 a novel C MYC binding protein that stimulates transcription activity of C MYC Genes to Cells 3 8 549 65 doi 10 1046 j 1365 2443 1998 00206 x PMID 9797456 S2CID 41886122 Izumi H Molander C Penn LZ Ishisaki A Kohno K Funa K April 2001 Mechanism for the transcriptional repression by c Myc on PDGF beta receptor Journal of Cell Science 114 Pt 8 1533 44 doi 10 1242 jcs 114 8 1533 PMID 11282029 Taira T Sawai M Ikeda M Tamai K Iguchi Ariga SM Ariga H August 1999 Cell cycle dependent switch of up and down regulation of human hsp70 gene expression by interaction between c Myc and CBF NF Y The Journal of Biological Chemistry 274 34 24270 9 doi 10 1074 jbc 274 34 24270 PMID 10446203 Uramoto H Izumi H Ise T Tada M Uchiumi T Kuwano M Yasumoto K Funa K Kohno K August 2002 p73 Interacts with c Myc to regulate Y box binding protein 1 expression The Journal of Biological Chemistry 277 35 31694 702 doi 10 1074 jbc M200266200 PMID 12080043 a b c d e f Liu X Tesfai J Evrard YA Dent SY Martinez E May 2003 c Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation The Journal of Biological Chemistry 278 22 20405 12 doi 10 1074 jbc M211795200 PMC 4031917 PMID 12660246 Mori K Maeda Y Kitaura H Taira T Iguchi Ariga SM Ariga H November 1998 MM 1 a novel c Myc associating protein that represses transcriptional activity of c Myc The Journal of Biological Chemistry 273 45 29794 800 doi 10 1074 jbc 273 45 29794 PMID 9792694 Fujioka Y Taira T Maeda Y Tanaka S Nishihara H Iguchi Ariga SM Nagashima K Ariga H November 2001 MM 1 a c Myc binding protein is a candidate for a tumor suppressor in leukemia lymphoma and tongue cancer The Journal of Biological Chemistry 276 48 45137 44 doi 10 1074 jbc M106127200 PMID 11567024 a b Feng XH Liang YY Liang M Zhai W Lin X January 2002 Direct interaction of c Myc with Smad2 and Smad3 to inhibit TGF beta mediated induction of the CDK inhibitor p15 Ink4B Molecular Cell 9 1 133 43 doi 10 1016 s1097 2765 01 00430 0 PMID 11804592 Otsuki Y Tanaka M Kamo T Kitanaka C Kuchino Y Sugimura H February 2003 Guanine nucleotide exchange factor Tiam1 directly binds to c Myc and interferes with c Myc mediated apoptosis in rat 1 fibroblasts The Journal of Biological Chemistry 278 7 5132 40 doi 10 1074 jbc M206733200 PMID 12446731 Gaubatz S Imhof A Dosch R Werner O Mitchell P Buettner R Eilers M April 1995 Transcriptional activation by Myc is under negative control by the transcription factor AP 2 The EMBO Journal 14 7 1508 19 doi 10 1002 j 1460 2075 1995 tb07137 x PMC 398238 PMID 7729426 Thomas LR Wang Q Grieb BC Phan J Foshage AM Sun Q Olejniczak ET Clark T Dey S Lorey S Alicie B Howard GC Cawthon B Ess KC Eischen CM Zhao Z Fesik SW Tansey WP May 2015 Interaction with WDR5 promotes target gene recognition and tumorigenesis by MYC Molecular Cell 58 3 440 52 doi 10 1016 j molcel 2015 02 028 PMC 4427524 PMID 25818646 Shrivastava A Saleque S Kalpana GV Artandi S Goff SP Calame K December 1993 Inhibition of transcriptional regulator Yin Yang 1 by association with c Myc Science 262 5141 1889 92 Bibcode 1993Sci 262 1889S doi 10 1126 science 8266081 PMID 8266081 Staller P Peukert K Kiermaier A Seoane J Lukas J Karsunky H Moroy T Bartek J Massague J Hanel F Eilers M April 2001 Repression of p15INK4b expression by Myc through association with Miz 1 Nature Cell Biology 3 4 392 9 doi 10 1038 35070076 PMID 11283613 S2CID 12696178 Peukert K Staller P Schneider A Carmichael G Hanel F Eilers M September 1997 An alternative pathway for gene regulation by Myc The EMBO Journal 16 18 5672 86 doi 10 1093 emboj 16 18 5672 PMC 1170199 PMID 9312026 PSICQUIC View ebi ac uk Retrieved 2019 05 02 Further reading editRuf IK Rhyne PW Yang H Borza CM Hutt Fletcher LM Cleveland JL Sample JT 2001 EBV Regulates c MYC Apoptosis and Tumorigenicity in Burkitt s Lymphoma Epstein Barr Virus and Human Cancer Current Topics in Microbiology and Immunology Vol 258 pp 153 60 doi 10 1007 978 3 642 56515 1 10 ISBN 978 3 642 62568 8 PMID 11443860 Luscher B October 2001 Function and regulation of the transcription factors of the Myc Max Mad network Gene 277 1 2 1 14 doi 10 1016 S0378 1119 01 00697 7 PMID 11602341 Hoffman B Amanullah A Shafarenko M Liebermann DA May 2002 The proto oncogene c myc in hematopoietic development and leukemogenesis Oncogene 21 21 3414 21 doi 10 1038 sj onc 1205400 PMID 12032779 S2CID 8720539 Pelengaris S Khan M Evan G October 2002 c MYC more than just a matter of life and death Nature Reviews Cancer 2 10 764 76 doi 10 1038 nrc904 PMID 12360279 S2CID 13226062 Nilsson JA Cleveland JL December 2003 Myc pathways provoking cell suicide and cancer Oncogene 22 56 9007 21 doi 10 1038 sj onc 1207261 PMID 14663479 S2CID 24758874 Dang CV O donnell KA Juopperi T September 2005 The great MYC escape in tumorigenesis Cancer Cell 8 3 177 8 doi 10 1016 j ccr 2005 08 005 PMID 16169462 Dang CV Li F Lee LA November 2005 Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability Cell Cycle 4 11 1465 6 doi 10 4161 cc 4 11 2121 PMID 16205115 Coller HA Forman JJ Legesse Miller A August 2007 Myc ed messages myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron PLOS Genetics 3 8 e146 doi 10 1371 journal pgen 0030146 PMC 1959363 PMID 17784791 Astrin SM Laurence J May 1992 Human immunodeficiency virus activates c myc and Epstein Barr virus in human B lymphocytes Annals of the New York Academy of Sciences 651 1 422 32 Bibcode 1992NYASA 651 422A doi 10 1111 j 1749 6632 1992 tb24642 x PMID 1318011 S2CID 31980333 Bernstein PL Herrick DJ Prokipcak RD Ross J April 1992 Control of c myc mRNA half life in vitro by a protein capable of binding to a coding region stability determinant Genes amp Development 6 4 642 54 doi 10 1101 gad 6 4 642 PMID 1559612 Iijima S Teraoka H Date T Tsukada K June 1992 DNA activated protein kinase in Raji Burkitt s lymphoma cells Phosphorylation of c Myc oncoprotein European Journal of Biochemistry 206 2 595 603 doi 10 1111 j 1432 1033 1992 tb16964 x PMID 1597196 Seth A Alvarez E Gupta S Davis RJ December 1991 A phosphorylation site located in the NH2 terminal domain of c Myc increases transactivation of gene expression The Journal of Biological Chemistry 266 35 23521 4 doi 10 1016 S0021 9258 18 54312 X PMID 1748630 Takahashi E Hori T O Connell P Leppert M White R 1991 Mapping of the MYC gene to band 8q24 12 q24 13 by R banding and distal to fra 8 q24 11 FRA8E by fluorescence in situ hybridization Cytogenetics and Cell Genetics 57 2 3 109 11 doi 10 1159 000133124 PMID 1914517 Blackwood EM Eisenman RN March 1991 Max a helix loop helix zipper protein that forms a sequence specific DNA binding complex with Myc Science 251 4998 1211 7 Bibcode 1991Sci 251 1211B doi 10 1126 science 2006410 PMID 2006410 Gazin C Rigolet M Briand JP Van Regenmortel MH Galibert F September 1986 Immunochemical detection of proteins related to the human c myc exon 1 The EMBO Journal 5 9 2241 50 doi 10 1002 j 1460 2075 1986 tb04491 x PMC 1167107 PMID 2430795 Luscher B Kuenzel EA Krebs EG Eisenman RN April 1989 Myc oncoproteins are phosphorylated by casein kinase II The EMBO Journal 8 4 1111 9 doi 10 1002 j 1460 2075 1989 tb03481 x PMC 400922 PMID 2663470 Finver SN Nishikura K Finger LR Haluska FG Finan J Nowell PC Croce CM May 1988 Sequence analysis of the MYC oncogene involved in the t 8 14 q24 q11 chromosome translocation in a human leukemia T cell line indicates that putative regulatory regions are not altered Proceedings of the National Academy of Sciences of the United States of America 85 9 3052 6 Bibcode 1988PNAS 85 3052F doi 10 1073 pnas 85 9 3052 PMC 280141 PMID 2834731 Showe LC Moore RC Erikson J Croce CM May 1987 MYC oncogene involved in a t 8 22 chromosome translocation is not altered in its putative regulatory regions Proceedings of the National Academy of Sciences of the United States of America 84 9 2824 8 Bibcode 1987PNAS 84 2824S doi 10 1073 pnas 84 9 2824 PMC 304752 PMID 3033665 Guilhot S Petridou B Syed Hussain S Galibert F December 1988 Nucleotide sequence 3 to the human c myc oncogene presence of a long inverted repeat Gene 72 1 2 105 8 doi 10 1016 0378 1119 88 90131 X PMID 3243428 Hann SR King MW Bentley DL Anderson CW Eisenman RN January 1988 A non AUG translational initiation in c myc exon 1 generates an N terminally distinct protein whose synthesis is disrupted in Burkitt s lymphomas Cell 52 2 185 95 doi 10 1016 0092 8674 88 90507 7 PMID 3277717 S2CID 3012009 External links editInterPro signatures for protein family IPR002418 IPR011598 IPR003327 The Myc Protein NCBI Human Myc protein Myc cancer gene myc Proto Oncogene Proteins at the U S National Library of Medicine Medical Subject Headings MeSH Generating iPS Cells from MEFS through Forced Expression of Sox 2 Oct 4 c Myc and Klf4 Drosophila Myc The Interactive Fly FactorBook C Myc PDBe KB provides an overview of all the structure information available in the PDB for Human Myc proto oncogene protein Retrieved from https en wikipedia org w index php title Myc amp oldid 1213479582, wikipedia, wiki, book, books, library,

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