MKL/megakaryoblastic leukemia 1 (also termed MRTFA/myocardin related transcription factor A) is a protein that in humans is encoded by the MKL1gene.[5][6][7][8]
The protein encoded by this gene is regulated by the actin cytoskeleton and is shuttled between the cytoplasm and the nucleus as a result of actin dynamics.[9] In the nucleus, it coactivates the transcription factor serum response factor,[10] a key regulator of smooth muscle cell differentiation, in an interaction mediated by its Basic domain. It is closely related to MKL2 and myocardin, with which it shares five key conserved structural domains.[11]
Clinical significanceedit
This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with acute megakaryocytic leukemia.[8] It also functions in the process of normal megakaryocyte maturation.[12]
Researchedit
Evalarted MKL1 expression is observed in breast cancer and can predict chemosensitivity and patient survival. MKL1 may be a promising biomarker of clinical value for breast cancer.[13]
^ abcGRCh38: Ensembl release 89: ENSG00000196588 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000042292 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, et al. (July 2001). "Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia". Nature Genetics. 28 (3): 220–221. doi:10.1038/90054. PMID 11431691. S2CID 36236342.
^Sasazuki T, Sawada T, Sakon S, Kitamura T, Kishi T, Okazaki T, et al. (August 2002). "Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death". The Journal of Biological Chemistry. 277 (32): 28853–28860. doi:10.1074/jbc.M203190200. PMID 12019265.
^Du KL, Chen M, Li J, Lepore JJ, Mericko P, Parmacek MS (April 2004). "Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells". The Journal of Biological Chemistry. 279 (17): 17578–17586. doi:10.1074/jbc.M400961200. PMID 14970199.
^Vartiainen MK, Guettler S, Larijani B, Treisman R (June 2007). "Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL". Science. 316 (5832): 1749–1752. Bibcode:2007Sci...316.1749V. doi:10.1126/science.1141084. PMID 17588931. S2CID 44910416.
^Miralles F, Posern G, Zaromytidou AI, Treisman R (May 2003). "Actin dynamics control SRF activity by regulation of its coactivator MAL". Cell. 113 (3): 329–342. doi:10.1016/S0092-8674(03)00278-2. PMID 12732141.
^Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. (November 2002). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–14860. Bibcode:2002PNAS...9914855W. doi:10.1073/pnas.222561499. PMC137508. PMID 12397177.
^Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, et al. (March 2009). "Role for MKL1 in megakaryocytic maturation". Blood. 113 (12): 2826–2834. doi:10.1182/blood-2008-09-180596. PMC2661865. PMID 19136660.
^Hua Y, Yang M (June 2022). "The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity". Bosnian Journal of Basic Medical Sciences. 22 (3): 382–394. doi:10.17305/bjbms.2021.6306. PMC9162751. PMID 34761735.
Further readingedit
Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, et al. (December 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–495. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (February 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, et al. (May 2001). "Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 98 (10): 5776–5779. Bibcode:2001PNAS...98.5776M. doi:10.1073/pnas.101001498. PMC33289. PMID 11344311.
Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, et al. (June 2001). "Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor". Cell. 105 (7): 851–862. doi:10.1016/S0092-8674(01)00404-4. PMID 11439182.
Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. (November 2002). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–14860. Bibcode:2002PNAS...9914855W. doi:10.1073/pnas.222561499. PMC137508. PMID 12397177.
Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, Prywes R (September 2003). "Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes". Molecular and Cellular Biology. 23 (18): 6597–6608. doi:10.1128/MCB.23.18.6597-6608.2003. PMC193697. PMID 12944485.
Selvaraj A, Prywes R (October 2003). "Megakaryoblastic leukemia-1/2, a transcriptional co-activator of serum response factor, is required for skeletal myogenic differentiation". The Journal of Biological Chemistry. 278 (43): 41977–41987. doi:10.1074/jbc.M305679200. PMID 14565952.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC514446. PMID 15302935.
Selvaraj A, Prywes R (August 2004). "Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent". BMC Molecular Biology. 5: 13. doi:10.1186/1471-2199-5-13. PMC516031. PMID 15329155.
Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, et al. (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC545604. PMID 15461802.
Hsiao HH, Yang MY, Liu YC, Hsiao HP, Tseng SB, Chao MC, et al. (May 2005). "RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient". American Journal of Hematology. 79 (1): 43–45. doi:10.1002/ajh.20298. PMID 15849773. S2CID 30859557.
Nakagawa K, Kuzumaki N (August 2005). "Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification". Genes to Cells. 10 (8): 835–850. doi:10.1111/j.1365-2443.2005.00880.x. PMID 16098147.
This article on a gene on human chromosome 22 is a stub. You can help Wikipedia by expanding it.
mkl1, megakaryoblastic, leukemia, also, termed, mrtfa, myocardin, related, transcription, factor, protein, that, humans, encoded, gene, mrtfaavailable, structurespdbortholog, search, pdbe, rcsblist, codes2kvu, 2kw9identifiersaliasesmrtfa, bsac, mrtf, megakaryo. MKL megakaryoblastic leukemia 1 also termed MRTFA myocardin related transcription factor A is a protein that in humans is encoded by the MKL1 gene 5 6 7 8 MRTFAAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes2KVU 2KW9IdentifiersAliasesMRTFA BSAC MAL MRTF A megakaryoblastic leukemia translocation 1 MKL MKL1 myocardin related transcription factor AExternal IDsOMIM 606078 MGI 2384495 HomoloGene 32487 GeneCards MRTFAGene location Human Chr Chromosome 22 human 1 Band22q13 1 q13 2Start40 410 281 bp 1 End40 636 719 bp 1 Gene location Mouse Chr Chromosome 15 mouse 2 Band15 15 E1Start80 896 482 bp 2 End81 074 958 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytepopliteal arterybone marrow cellsbloodstromal cell of endometriumleft uterine tubesural nervecanal of the cervixleft coronary arterythymusTop expressed inolfactory tuberclebloodinternal carotid arterymolarsubiculumexternal carotid arteryknee jointentorhinal cortexsuperior frontal gyrusnucleus accumbensMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functiontranscription coactivator activity actin monomer binding leucine zipper domain binding protein binding actin bindingCellular componentcytoplasm nucleoplasm nucleus cytosolBiological processregulation of transcription DNA templated smooth muscle cell differentiation transcription DNA templated positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II actin cytoskeleton organizationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez57591223701EnsemblENSG00000196588ENSMUSG00000042292UniProtQ969V6Q8K4J6RefSeq mRNA NM 001282660NM 001282661NM 001282662NM 020831NM 001318139NM 001082536NM 153049RefSeq protein NP 001269589NP 001269590NP 001269591NP 001305068NP 065882NP 001076005NP 694629Location UCSC Chr 22 40 41 40 64 MbChr 15 80 9 81 07 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 Research 4 See also 5 References 6 Further readingFunction editThe protein encoded by this gene is regulated by the actin cytoskeleton and is shuttled between the cytoplasm and the nucleus as a result of actin dynamics 9 In the nucleus it coactivates the transcription factor serum response factor 10 a key regulator of smooth muscle cell differentiation in an interaction mediated by its Basic domain It is closely related to MKL2 and myocardin with which it shares five key conserved structural domains 11 Clinical significance editThis gene is involved in a specific translocation event that creates a fusion of this gene and the RNA binding motif protein 15 gene This translocation has been associated with acute megakaryocytic leukemia 8 It also functions in the process of normal megakaryocyte maturation 12 Research editEvalarted MKL1 expression is observed in breast cancer and can predict chemosensitivity and patient survival MKL1 may be a promising biomarker of clinical value for breast cancer 13 See also editSerum response factorReferences edit a b c GRCh38 Ensembl release 89 ENSG00000196588 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000042292 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Ma Z Morris SW Valentine V Li M Herbrick JA Cui X et al July 2001 Fusion of two novel genes RBM15 and MKL1 in the t 1 22 p13 q13 of acute megakaryoblastic leukemia Nature Genetics 28 3 220 221 doi 10 1038 90054 PMID 11431691 S2CID 36236342 Sasazuki T Sawada T Sakon S Kitamura T Kishi T Okazaki T et al August 2002 Identification of a novel transcriptional activator BSAC by a functional cloning to inhibit tumor necrosis factor induced cell death The Journal of Biological Chemistry 277 32 28853 28860 doi 10 1074 jbc M203190200 PMID 12019265 Du KL Chen M Li J Lepore JJ Mericko P Parmacek MS April 2004 Megakaryoblastic leukemia factor 1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells The Journal of Biological Chemistry 279 17 17578 17586 doi 10 1074 jbc M400961200 PMID 14970199 a b Entrez Gene MKL1 megakaryoblastic leukemia translocation 1 Vartiainen MK Guettler S Larijani B Treisman R June 2007 Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL Science 316 5832 1749 1752 Bibcode 2007Sci 316 1749V doi 10 1126 science 1141084 PMID 17588931 S2CID 44910416 Miralles F Posern G Zaromytidou AI Treisman R May 2003 Actin dynamics control SRF activity by regulation of its coactivator MAL Cell 113 3 329 342 doi 10 1016 S0092 8674 03 00278 2 PMID 12732141 Wang DZ Li S Hockemeyer D Sutherland L Wang Z Schratt G et al November 2002 Potentiation of serum response factor activity by a family of myocardin related transcription factors Proceedings of the National Academy of Sciences of the United States of America 99 23 14855 14860 Bibcode 2002PNAS 9914855W doi 10 1073 pnas 222561499 PMC 137508 PMID 12397177 Cheng EC Luo Q Bruscia EM Renda MJ Troy JA Massaro SA et al March 2009 Role for MKL1 in megakaryocytic maturation Blood 113 12 2826 2834 doi 10 1182 blood 2008 09 180596 PMC 2661865 PMID 19136660 Hua Y Yang M June 2022 The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity Bosnian Journal of Basic Medical Sciences 22 3 382 394 doi 10 17305 bjbms 2021 6306 PMC 9162751 PMID 34761735 Further reading editNakajima D Okazaki N Yamakawa H Kikuno R Ohara O Nagase T June 2002 Construction of expression ready cDNA clones for KIAA genes manual curation of 330 KIAA cDNA clones DNA Research 9 3 99 106 doi 10 1093 dnares 9 3 99 PMID 12168954 Dunham I Shimizu N Roe BA Chissoe S Hunt AR Collins JE et al December 1999 The DNA sequence of human chromosome 22 Nature 402 6761 489 495 Bibcode 1999Natur 402 489D doi 10 1038 990031 PMID 10591208 Nagase T Kikuno R Ishikawa KI Hirosawa M Ohara O February 2000 Prediction of the coding sequences of unidentified human genes XVI The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro DNA Research 7 1 65 73 doi 10 1093 dnares 7 1 65 PMID 10718198 Mercher T Coniat MB Monni R Mauchauffe M Nguyen Khac F Gressin L et al May 2001 Involvement of a human gene related to the Drosophila spen gene in the recurrent t 1 22 translocation of acute megakaryocytic leukemia Proceedings of the National Academy of Sciences of the United States of America 98 10 5776 5779 Bibcode 2001PNAS 98 5776M doi 10 1073 pnas 101001498 PMC 33289 PMID 11344311 Wang D Chang PS Wang Z Sutherland L Richardson JA Small E et al June 2001 Activation of cardiac gene expression by myocardin a transcriptional cofactor for serum response factor Cell 105 7 851 862 doi 10 1016 S0092 8674 01 00404 4 PMID 11439182 Wang DZ Li S Hockemeyer D Sutherland L Wang Z Schratt G et al November 2002 Potentiation of serum response factor activity by a family of myocardin related transcription factors Proceedings of the National Academy of Sciences of the United States of America 99 23 14855 14860 Bibcode 2002PNAS 9914855W doi 10 1073 pnas 222561499 PMC 137508 PMID 12397177 Cen B Selvaraj A Burgess RC Hitzler JK Ma Z Morris SW Prywes R September 2003 Megakaryoblastic leukemia 1 a potent transcriptional coactivator for serum response factor SRF is required for serum induction of SRF target genes Molecular and Cellular Biology 23 18 6597 6608 doi 10 1128 MCB 23 18 6597 6608 2003 PMC 193697 PMID 12944485 Selvaraj A Prywes R October 2003 Megakaryoblastic leukemia 1 2 a transcriptional co activator of serum response factor is required for skeletal myogenic differentiation The Journal of Biological Chemistry 278 43 41977 41987 doi 10 1074 jbc M305679200 PMID 14565952 Beausoleil SA Jedrychowski M Schwartz D Elias JE Villen J Li J et al August 2004 Large scale characterization of HeLa cell nuclear phosphoproteins Proceedings of the National Academy of Sciences of the United States of America 101 33 12130 12135 Bibcode 2004PNAS 10112130B doi 10 1073 pnas 0404720101 PMC 514446 PMID 15302935 Selvaraj A Prywes R August 2004 Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent BMC Molecular Biology 5 13 doi 10 1186 1471 2199 5 13 PMC 516031 PMID 15329155 Collins JE Wright CL Edwards CA Davis MP Grinham JA Cole CG et al 2005 A genome annotation driven approach to cloning the human ORFeome Genome Biology 5 10 R84 doi 10 1186 gb 2004 5 10 r84 PMC 545604 PMID 15461802 Hsiao HH Yang MY Liu YC Hsiao HP Tseng SB Chao MC et al May 2005 RBM15 MKL1 OTT MAL fusion transcript in an adult acute myeloid leukemia patient American Journal of Hematology 79 1 43 45 doi 10 1002 ajh 20298 PMID 15849773 S2CID 30859557 Nakagawa K Kuzumaki N August 2005 Transcriptional activity of megakaryoblastic leukemia 1 MKL1 is repressed by SUMO modification Genes to Cells 10 8 835 850 doi 10 1111 j 1365 2443 2005 00880 x PMID 16098147 nbsp This article on a gene on human chromosome 22 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title MKL1 amp oldid 1188143861, wikipedia, wiki, book, books, library,
