Protein-coding gene in the species Homo sapiens
Lymphoid enhancer-binding factor 1 (LEF1 ) is a protein that in humans is encoded by the LEF1 gene .[5] TCF/LEF ) family.
Function [ edit ] 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 [ edit ] LEF1 is highly overexpressed and associated with disease progression and poor prognosis in B-cell chronic lymphocytic leukemia [7] colorectal cancer .[8] [9]
Interactions [ edit ] Lymphoid enhancer-binding factor 1 has been shown to interact with:
References [ edit ]
^ a b c GRCh38: Ensembl release 89: ENSG00000138795 - Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027985 - 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 .^ 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 . ^ "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1" .^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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 . ^ 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. Bibcode :1996Natur.382..638B . doi :10.1038/382638a0 . PMID 8757136 . S2CID 4369341 . ^ a b c 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. Bibcode :2000PNAS...97.8358L . doi :10.1073/pnas.150152697 PMC 26952 PMID 10890911 . ^ Barolo S, Posakony JW (May 2002). "Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling" . Genes & Development . 16 (10). Cold Spring Harbor Laboratory Press & The Genetics Society : 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). ^ 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 . ^ 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 . ^ 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 [ edit ]
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 (1): 143–151. Bibcode :2007NYASA1106..143S . 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. Bibcode :1996Natur.382..638B . 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. Bibcode :1998PNAS...9511590L . 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. Bibcode :2000PNAS...97.8358L . 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 [ edit ] This article incorporates text from the United States National Library of Medicine , which is in the public domain .
(1) Basic domains
(1.1) Basic leucine zipper (bZIP )(1.2) Basic helix-loop-helix (bHLH )
Group A Group B Group CPAS Group D Group E Group F
(1.3) bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4) β-Scaffold factors with minor groove contacts
(0) Other transcription factors
