Lymphoid enhancer-binding factor 1

Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene.^[5] It's a member of T cell factor/lymphoid enhancer factor (TCF/LEF) family.

LEF1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2LEF, 3OUW, 3OUX
Identifiers
Aliases	LEF1, LEF-1, TCF10, TCF1ALPHA, TCF7L3, lymphoid enhancer binding factor 1
External IDs	MGI: 96770 HomoloGene: 7813 GeneCards: LEF1
Gene location (Human) Chr. Chromosome 4 (human)^[1] Band 4q25 Start 108,047,545 bp^[1] End 108,168,956 bp^[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)^[2] Band 3 G3|3 60.78 cM Start 130,904,120 bp^[2] End 131,018,005 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in thymus lymph node tibia oocyte secondary oocyte blood appendix endometrium caput epididymis sperm Top expressed in thymus maxillary prominence blood hair follicle dental papilla secondary oocyte primitive streak endocardial cushion spermatocyte lateral geniculate nucleus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific histone deacetylase binding armadillo repeat domain binding estrogen receptor binding RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor binding estrogen receptor activity gamma-catenin binding histone binding C2H2 zinc finger domain binding chromatin binding cysteine-type endopeptidase inhibitor activity involved in apoptotic process protein binding DNA binding, bending DNA binding sequence-specific DNA binding transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding beta-catenin binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm nucleus transcription regulator complex beta-catenin-TCF complex nucleoplasm protein-DNA complex Biological process somitogenesis tongue development paraxial mesoderm formation regulation of transcription by RNA polymerase II negative regulation of DNA binding T cell receptor V(D)J recombination transcription by RNA polymerase II cellular response to cytokine stimulus mammary gland development negative regulation of interleukin-13 production odontogenesis of dentin-containing tooth apoptotic process involved in blood vessel morphogenesis cell chemotaxis negative regulation of canonical Wnt signaling pathway face morphogenesis neutrophil differentiation negative regulation of interleukin-5 production regulation of transcription, DNA-templated dentate gyrus development apoptotic process involved in morphogenesis transcription, DNA-templated positive regulation of transcription, DNA-templated positive regulation of cell growth regulation of Wnt signaling pathway embryonic limb morphogenesis hypothalamus development branching involved in blood vessel morphogenesis trachea gland development regulation of striated muscle tissue development positive regulation of cell-cell adhesion forebrain neuroblast division eye pigmentation negative regulation of apoptotic process sprouting angiogenesis negative regulation of transcription by RNA polymerase II positive regulation of epithelial to mesenchymal transition BMP signaling pathway positive regulation of cell cycle process osteoblast differentiation histone H3 acetylation formation of radial glial scaffolds positive regulation of granulocyte differentiation alpha-beta T cell differentiation canonical Wnt signaling pathway negative regulation of transcription, DNA-templated sensory perception of taste cellular response to interleukin-4 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process cell development negative regulation of cell-cell adhesion negative regulation of interleukin-4 production negative regulation of striated muscle tissue development positive regulation of cell migration Wnt signaling pathway T-helper 1 cell differentiation positive regulation of cell proliferation in bone marrow anatomical structure regression chorio-allantoic fusion negative regulation of apoptotic process in bone marrow cell B cell proliferation positive regulation of gene expression vasculature development forebrain radial glial cell differentiation neural crest cell migration positive regulation of cell population proliferation forebrain neuron differentiation histone H4 acetylation hippocampus development positive regulation of transcription by RNA polymerase II Wnt signaling pathway, calcium modulating pathway steroid hormone mediated signaling pathway odontoblast differentiation beta-catenin-TCF complex assembly epithelial to mesenchymal transition regulation of cell-cell adhesion secondary palate development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 51176 16842 Ensembl ENSG00000138795 ENSMUSG00000027985 UniProt Q9UJU2 Q659G9 P27782 RefSeq (mRNA) NM_001130713 NM_001130714 NM_001166119 NM_016269 NM_001276402 NM_001276403 NM_010703 NM_001379059 NM_001379060 NM_001379061 NM_001379062 RefSeq (protein) NP_001124185 NP_001124186 NP_001159591 NP_057353 NP_057353.1 NP_001263331 NP_001263332 NP_034833 NP_001365988 NP_001365989 NP_001365990 NP_001365991 Location (UCSC) Chr 4: 108.05 – 108.17 Mb Chr 3: 130.9 – 131.02 Mb PubMed search ^[3] ^[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Lymphoid enhancer-binding factor-1 (LEF1) is a 48-kD nuclear protein that is expressed in pre-B and T cells. It binds to a functionally important site in the T-cell receptor-alpha (TCRA) enhancer and confers maximal enhancer activity. LEF1 belongs to a family of regulatory proteins that share homology with high mobility group protein-1 (HMG1).^[6]

Clinical significance

LEF1 is highly overexpressed and associated with disease progression and poor prognosis in B-cell chronic lymphocytic leukemia^[7] and other kinds of malignancies like colorectal cancer.^[8] It is also a promising potential drug target.^[9]

Interactions

Lymphoid enhancer-binding factor 1 has been shown to interact with:

• ALX4,^[10]
• AML-1,^[11]
• Catenin beta-1/β-catenin/CTNNB1,^{[12][13][14][15]} including transgenically,^[16]
• EP300,^[17]
• MITF^[18]
• PIAS4,^[19]
• SMAD2,^[15] and
• SMAD3.^[15]

References

1. GRCh38: Ensembl release 89: ENSG00000138795 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027985 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Milatovich A, Travis A, Grosschedl R, Francke U (December 1991). "Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf". Genomics. 11 (4): 1040–1048. doi:10.1016/0888-7543(91)90030-I. PMID 1783375.
6. "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1".
7. Erdfelder F, Hertweck M, Filipovich A, Uhrmacher S, Kreuzer KA (January 2010). "High lymphoid enhancer-binding factor-1 expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia". Hematology Reports. 2 (1): e3. doi:10.4081/hr.2010.e3. PMC 3222268. PMID 22184516.
8. Eskandari E, Mahjoubi F, Motalebzadeh J (December 2018). "An integrated study on TFs and miRNAs in colorectal cancer metastasis and evaluation of three co-regulated candidate genes as prognostic markers". Gene. 679: 150–159. doi:10.1016/j.gene.2018.09.003. PMID 30193961. S2CID 52172531.
9. Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlösser A, et al. (April 2010). "Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo". Neoplasia. 12 (4): 326–335. doi:10.1593/neo.91972. PMC 2847740. PMID 20360943.
10. Boras K, Hamel PA (January 2002). "Alx4 binding to LEF-1 regulates N-CAM promoter activity". The Journal of Biological Chemistry. 277 (2): 1120–1127. doi:10.1074/jbc.M109912200. PMID 11696550.
11. Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW (January 2000). "A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia". The Journal of Biological Chemistry. 275 (1): 651–656. doi:10.1074/jbc.275.1.651. PMID 10617663.
12. Edlund S, Lee SY, Grimsby S, Zhang S, Aspenström P, Heldin CH, Landström M (February 2005). "Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis". Molecular and Cellular Biology. 25 (4): 1475–1488. doi:10.1128/MCB.25.4.1475-1488.2005. PMC 548008. PMID 15684397.
13. Grueneberg DA, Pablo L, Hu KQ, August P, Weng Z, Papkoff J (June 2003). "A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway". Molecular and Cellular Biology. 23 (11): 3936–3950. doi:10.1128/MCB.23.11.3936-3950.2003. PMC 155208. PMID 12748295.
14. Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W (August 1996). "Functional interaction of beta-catenin with the transcription factor LEF-1". Nature. 382 (6592): 638–642. doi:10.1038/382638a0. PMID 8757136. S2CID 4369341.
15. Labbé E, Letamendia A, Attisano L (July 2000). "Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways". Proceedings of the National Academy of Sciences of the United States of America. 97 (15): 8358–8363. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911.
16. Barolo S, Posakony JW (May 2002). "Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling". Genes & Development. Cold Spring Harbor Laboratory Press & The Genetics Society. 16 (10): 1167–1181. doi:10.1101/gad.976502. PMID 12023297. S2CID 14376483. p. 1170: In ... zebrafish, reporter transgenes containing the TOPFLASH promoter are expressed in certain Wnt-responsive cell types (...Dorsky et al. 2002).
17. Hecht A, Stemmler MP (February 2003). "Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4". The Journal of Biological Chemistry. 278 (6): 3776–3785. doi:10.1074/jbc.M210081200. PMID 12446687.
18. Yasumoto K, Takeda K, Saito H, Watanabe K, Takahashi K, Shibahara S (June 2002). "Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling". The EMBO Journal. 21 (11): 2703–2714. doi:10.1093/emboj/21.11.2703. PMC 126018. PMID 12032083.
19. Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R (December 2001). "PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies". Genes & Development. 15 (23): 3088–3103. doi:10.1101/gad.944801. PMC 312834. PMID 11731474.

Further reading

• Waterman ML (2004). "Lymphoid enhancer factor/T cell factor expression in colorectal cancer". Cancer and Metastasis Reviews. 23 (1–2): 41–52. doi:10.1023/A:1025858928620. PMID 15000148. S2CID 20996511.
• Skokowa J, Welte K (June 2007). "LEF-1 is a decisive transcription factor in neutrophil granulopoiesis". Annals of the New York Academy of Sciences. 1106: 143–151. doi:10.1196/annals.1392.012. PMID 17360796. S2CID 30579011.
• Travis A, Amsterdam A, Belanger C, Grosschedl R (May 1991). "LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]". Genes & Development. 5 (5): 880–894. doi:10.1101/gad.5.5.880. PMID 1827423.
• van de Wetering M, Oosterwegel M, Dooijes D, Clevers H (January 1991). "Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box". The EMBO Journal. 10 (1): 123–132. doi:10.1002/j.1460-2075.1991.tb07928.x. PMC 452620. PMID 1989880.
• Waterman ML, Fischer WH, Jones KA (April 1991). "A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer". Genes & Development. 5 (4): 656–669. doi:10.1101/gad.5.4.656. PMID 2010090.
• Zhou P, Byrne C, Jacobs J, Fuchs E (March 1995). "Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate". Genes & Development. 9 (6): 700–713. doi:10.1101/gad.9.6.700. PMID 7537238.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Prieve MG, Guttridge KL, Munguia JE, Waterman ML (March 1996). "The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins". The Journal of Biological Chemistry. 271 (13): 7654–7658. doi:10.1074/jbc.271.13.7654. PMID 8631802.
• Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W (August 1996). "Functional interaction of beta-catenin with the transcription factor LEF-1". Nature. 382 (6592): 638–642. doi:10.1038/382638a0. PMID 8757136. S2CID 4369341.
• Bagga R, Emerson BM (March 1997). "An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro". Genes & Development. 11 (5): 629–639. doi:10.1101/gad.11.5.629. PMID 9119227.
• Bruhn L, Munnerlyn A, Grosschedl R (March 1997). "ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function". Genes & Development. 11 (5): 640–653. doi:10.1101/gad.11.5.640. PMID 9119228.
• Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D (September 1997). "A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus". Genes & Development. 11 (18): 2359–2370. doi:10.1101/gad.11.18.2359. PMC 316518. PMID 9308964.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Korinek V, Barker N, Willert K, Molenaar M, Roose J, Wagenaar G, et al. (March 1998). "Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse". Molecular and Cellular Biology. 18 (3): 1248–1256. doi:10.1128/MCB.18.3.1248. PMC 108837. PMID 9488439.
• Prieve MG, Guttridge KL, Munguia J, Waterman ML (August 1998). "Differential importin-alpha recognition and nuclear transport by nuclear localization signals within the high-mobility-group DNA binding domains of lymphoid enhancer factor 1 and T-cell factor 1". Molecular and Cellular Biology. 18 (8): 4819–4832. doi:10.1128/MCB.18.8.4819. PMC 109067. PMID 9671491.
• Levanon D, Goldstein RE, Bernstein Y, Tang H, Goldenberg D, Stifani S, et al. (September 1998). "Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11590–11595. doi:10.1073/pnas.95.20.11590. PMC 21685. PMID 9751710.
• Hovanes K, Li TW, Waterman ML (May 2000). "The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing". Nucleic Acids Research. 28 (9): 1994–2003. doi:10.1093/nar/28.9.1994. PMC 103301. PMID 10756202.
• Labbé E, Letamendia A, Attisano L (July 2000). "Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and wnt pathways". Proceedings of the National Academy of Sciences of the United States of America. 97 (15): 8358–8363. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911.
• Brantjes H, Roose J, van De Wetering M, Clevers H (April 2001). "All Tcf HMG box transcription factors interact with Groucho-related co-repressors". Nucleic Acids Research. 29 (7): 1410–1419. doi:10.1093/nar/29.7.1410. PMC 31284. PMID 11266540.

External links

• LEF1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.