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] It is a member of T cell factor/lymphoid enhancer factor (TCF/LEF ) family.
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] and other kinds of malignancies like colorectal cancer .[ 8] It is also a promising potential drug target.[ 9]
Lymphoid enhancer-binding factor 1 has been shown to interact with:
^ 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 .
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 .
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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 C bHLH-PAS Group D Group E Group F bHLH-COE
(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