Biology:Lymphoid enhancer-binding factor 1
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Short description: Protein-coding gene in the species Homo sapiens
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Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene.[1] It is a member of T cell factor/lymphoid enhancer factor (TCF/LEF) family.
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).[2]
Clinical significance
LEF1 is highly overexpressed and associated with disease progression and poor prognosis in B-cell chronic lymphocytic leukemia[3] and other kinds of malignancies like colorectal cancer.[4] It is also a promising potential drug target.[5]
Interactions
Lymphoid enhancer-binding factor 1 has been shown to interact with:
- ALX4,[6]
- AML-1,[7]
- Catenin beta-1/β-catenin/CTNNB1,[8][9][10][11] including transgenically,[12]
- EP300,[13]
- MITF[14]
- PIAS4,[15]
- SMAD2,[11] and
- SMAD3.[11]
References
- ↑ "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. December 1991. doi:10.1016/0888-7543(91)90030-I. PMID 1783375.
- ↑ "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51176.
- ↑ "High lymphoid enhancer-binding factor-1 expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia". Hematology Reports 2 (1): e3. January 2010. doi:10.4081/hr.2010.e3. PMID 22184516.
- ↑ "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. December 2018. doi:10.1016/j.gene.2018.09.003. PMID 30193961.
- ↑ "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. April 2010. doi:10.1593/neo.91972. PMID 20360943.
- ↑ "Alx4 binding to LEF-1 regulates N-CAM promoter activity". The Journal of Biological Chemistry 277 (2): 1120–1127. January 2002. doi:10.1074/jbc.M109912200. PMID 11696550.
- ↑ "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. January 2000. doi:10.1074/jbc.275.1.651. PMID 10617663.
- ↑ "Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis". Molecular and Cellular Biology 25 (4): 1475–1488. February 2005. doi:10.1128/MCB.25.4.1475-1488.2005. PMID 15684397.
- ↑ "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. June 2003. doi:10.1128/MCB.23.11.3936-3950.2003. PMID 12748295.
- ↑ "Functional interaction of beta-catenin with the transcription factor LEF-1". Nature 382 (6592): 638–642. August 1996. doi:10.1038/382638a0. PMID 8757136. Bibcode: 1996Natur.382..638B.
- ↑ 11.0 11.1 11.2 "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. July 2000. doi:10.1073/pnas.150152697. PMID 10890911. Bibcode: 2000PNAS...97.8358L.
- ↑ "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. May 2002. doi:10.1101/gad.976502. PMID 12023297. "In ... zebrafish, reporter transgenes containing the TOPFLASH promoter are expressed in certain Wnt-responsive cell types (...Dorsky et al. 2002).".
- ↑ "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. February 2003. doi:10.1074/jbc.M210081200. PMID 12446687.
- ↑ "Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling". The EMBO Journal 21 (11): 2703–2714. June 2002. doi:10.1093/emboj/21.11.2703. PMID 12032083.
- ↑ "PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies". Genes & Development 15 (23): 3088–3103. December 2001. doi:10.1101/gad.944801. PMID 11731474.
Further reading
- "Lymphoid enhancer factor/T cell factor expression in colorectal cancer". Cancer and Metastasis Reviews 23 (1–2): 41–52. 2004. doi:10.1023/A:1025858928620. PMID 15000148. https://zenodo.org/record/895454.
- "LEF-1 is a decisive transcription factor in neutrophil granulopoiesis". Annals of the New York Academy of Sciences 1106 (1): 143–151. June 2007. doi:10.1196/annals.1392.012. PMID 17360796. Bibcode: 2007NYASA1106..143S.
- "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. May 1991. doi:10.1101/gad.5.5.880. PMID 1827423.
- "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. January 1991. doi:10.1002/j.1460-2075.1991.tb07928.x. PMID 1989880.
- "A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer". Genes & Development 5 (4): 656–669. April 1991. doi:10.1101/gad.5.4.656. PMID 2010090.
- "Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate". Genes & Development 9 (6): 700–713. March 1995. doi:10.1101/gad.9.6.700. PMID 7537238.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–174. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "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. March 1996. doi:10.1074/jbc.271.13.7654. PMID 8631802.
- "Functional interaction of beta-catenin with the transcription factor LEF-1". Nature 382 (6592): 638–642. August 1996. doi:10.1038/382638a0. PMID 8757136. Bibcode: 1996Natur.382..638B.
- "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. March 1997. doi:10.1101/gad.11.5.629. PMID 9119227.
- "ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function". Genes & Development 11 (5): 640–653. March 1997. doi:10.1101/gad.11.5.640. PMID 9119228.
- "A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus". Genes & Development 11 (18): 2359–2370. September 1997. doi:10.1101/gad.11.18.2359. PMID 9308964.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–156. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "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. March 1998. doi:10.1128/MCB.18.3.1248. PMID 9488439.
- "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. August 1998. doi:10.1128/MCB.18.8.4819. PMID 9671491.
- "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. September 1998. doi:10.1073/pnas.95.20.11590. PMID 9751710. Bibcode: 1998PNAS...9511590L.
- "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. May 2000. doi:10.1093/nar/28.9.1994. PMID 10756202.
- "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. July 2000. doi:10.1073/pnas.150152697. PMID 10890911. Bibcode: 2000PNAS...97.8358L.
- "All Tcf HMG box transcription factors interact with Groucho-related co-repressors". Nucleic Acids Research 29 (7): 1410–1419. April 2001. doi:10.1093/nar/29.7.1410. PMID 11266540.
External links
- LEF1+protein,+human at the US 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.
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