| 释义 |
- Function
- Clinical significance
- Interactions
- References
- Further reading
- External links
{{Infobox_gene}}Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene.[1] 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] InteractionsLymphoid enhancer-binding factor 1 has been shown to interact with: - ALX4,[6]
- AML-1,[7]
- CTNNB1,[8][9][10][11]
- EP300,[12]
- MITF[13]
- PIAS4,[14]
- SMAD2,[11] and
- SMAD3.[11]
References1. ^{{cite journal |vauthors=Milatovich A, Travis A, Grosschedl R, Francke U | title = Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf | journal = Genomics | volume = 11 | issue = 4 | pages = 1040–8 |date=Mar 1992 | pmid = 1783375 | pmc = | doi =10.1016/0888-7543(91)90030-I }}
2. ^{{cite web | title = Entrez Gene: LEF1 lymphoid enhancer-binding factor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51176| accessdate = }}
3. ^{{cite journal |vauthors=Erdfelder F, Hertweck M, Filipovich A, Uhrmacher S, Kreuzer KA | title = High lymphoid enhancer- binding factor-1 expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia| journal = Hematology Reports| volume = 2| issue = 1| page = 3| year = 2010 | month = | pmid = 22184516| pmc = 3222268| doi = 10.4081/hr.2010.e3| issn = }}
4. ^{{cite journal |vauthors=Eskandari E, Mahjoubi F, Motalebzadeh J |title=An integrated study on TFs and miRNAs in colorectal cancer metastasis and evaluation of three co-regulated candidate genes as prognostic markers |journal=Gene |date=30 December 2018 |volume=679 |pages=150–159 |doi=10.1016/j.gene.2018.09.003 |pmid=30193961 }}
5. ^{{cite journal |vauthors=Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlösser A, Schmitt EK, Hallek M, Kreuzer KA | title = Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo | journal = Neoplasia | volume = 12 | issue = 4 | pages = 326–35 |date=April 2010 | pmid = 20360943 | pmc = 2847740 | doi = 10.1593/neo.91972 }}
6. ^{{cite journal |vauthors=Boras K, Hamel PA | title = Alx4 binding to LEF-1 regulates N-CAM promoter activity | journal = J. Biol. Chem. | volume = 277 | issue = 2 | pages = 1120–7 |date=January 2002 | pmid = 11696550 | doi = 10.1074/jbc.M109912200 }}
7. ^{{cite journal |vauthors=Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW | title = A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia | journal = J. Biol. Chem. | volume = 275 | issue = 1 | pages = 651–6 |date=January 2000 | pmid = 10617663 | doi =10.1074/jbc.275.1.651 }}
8. ^{{cite journal |vauthors=Edlund S, Lee SY, Grimsby S, Zhang S, Aspenström P, Heldin CH, Landström M | title = Interaction between Smad7 and beta-catenin: importance for transforming growth factor beta-induced apoptosis | journal = Mol. Cell. Biol. | volume = 25 | issue = 4 | pages = 1475–88 |date=February 2005 | pmid = 15684397 | pmc = 548008 | doi = 10.1128/MCB.25.4.1475-1488.2005 }}
9. ^{{cite journal |vauthors=Grueneberg DA, Pablo L, Hu KQ, August P, Weng Z, Papkoff J | title = A functional screen in human cells identifies UBF2 as an RNA polymerase II transcription factor that enhances the beta-catenin signaling pathway | journal = Mol. Cell. Biol. | volume = 23 | issue = 11 | pages = 3936–50 |date=June 2003 | pmid = 12748295 | pmc = 155208 | doi =10.1128/MCB.23.11.3936-3950.2003 }}
10. ^{{cite journal |vauthors=Behrens J, von Kries JP, Kühl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W | title = Functional interaction of beta-catenin with the transcription factor LEF-1 | journal = Nature | volume = 382 | issue = 6592 | pages = 638–42 |date=August 1996 | pmid = 8757136 | doi = 10.1038/382638a0 }}
11. ^1 2 {{cite journal |vauthors=Labbé E, Letamendia A, Attisano L | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 15 | pages = 8358–63 |date=July 2000 | pmid = 10890911 | pmc = 26952 | doi = 10.1073/pnas.150152697 }}
12. ^{{cite journal |vauthors=Hecht A, Stemmler MP | title = Identification of a promoter-specific transcriptional activation domain at the C terminus of the Wnt effector protein T-cell factor 4 | journal = J. Biol. Chem. | volume = 278 | issue = 6 | pages = 3776–85 |date=February 2003 | pmid = 12446687 | doi = 10.1074/jbc.M210081200 }}
13. ^{{cite journal |vauthors=Yasumoto K, Takeda K, Saito H, Watanabe K, Takahashi K, Shibahara S | title = Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling | journal = EMBO J. | volume = 21 | issue = 11 | pages = 2703–14 |date=June 2002 | pmid = 12032083 | pmc = 126018 | doi = 10.1093/emboj/21.11.2703 }}
14. ^{{cite journal |vauthors=Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R | title = PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies | journal = Genes Dev. | volume = 15 | issue = 23 | pages = 3088–103 |date=December 2001 | pmid = 11731474 | pmc = 312834 | doi =10.1101/gad.944801 }}
Further reading{{Refbegin|2}}- {{cite journal | author=Waterman ML |title=Lymphoid enhancer factor/T cell factor expression in colorectal cancer. |journal=Cancer Metastasis Rev. |volume=23 |issue= 1–2 |pages= 41–52 |year= 2004 |pmid= 15000148 |doi=10.1023/A:1025858928620|url=https://zenodo.org/record/895454 }}
- {{cite journal |vauthors=Skokowa J, Welte K |title=LEF-1 is a decisive transcription factor in neutrophil granulopoiesis |journal=Ann. N. Y. Acad. Sci. |volume=1106 |issue= |pages= 143–51 |year= 2007 |pmid= 17360796 |doi= 10.1196/annals.1392.012 }}
- {{cite journal |vauthors=Travis A, Amsterdam A, Belanger C, Grosschedl R |title=LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected] |journal=Genes Dev. |volume=5 |issue= 5 |pages= 880–94 |year= 1991 |pmid= 1827423 |doi=10.1101/gad.5.5.880 }}
- {{cite journal |vauthors=van de Wetering M, Oosterwegel M, Dooijes D, Clevers H |title=Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box |journal=EMBO J. |volume=10 |issue= 1 |pages= 123–32 |year= 1991 |pmid= 1989880 |doi= 10.1002/j.1460-2075.1991.tb07928.x| pmc=452620 }}
- {{cite journal |vauthors=Waterman ML, Fischer WH, Jones KA |title=A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer |journal=Genes Dev. |volume=5 |issue= 4 |pages= 656–69 |year= 1991 |pmid= 2010090 |doi=10.1101/gad.5.4.656 }}
- {{cite journal |vauthors=Zhou P, Byrne C, Jacobs J, Fuchs E |title=Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate |journal=Genes Dev. |volume=9 |issue= 6 |pages= 700–13 |year= 1995 |pmid= 7537238 |doi=10.1101/gad.9.6.700 }}
- {{cite journal |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
- {{cite journal |vauthors=Prieve MG, Guttridge KL, Munguia JE, Waterman ML |title=The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins |journal=J. Biol. Chem. |volume=271 |issue= 13 |pages= 7654–8 |year= 1996 |pmid= 8631802 |doi=10.1074/jbc.271.13.7654 }}
- {{cite journal |vauthors=Behrens J, von Kries JP, Kühl M, etal |title=Functional interaction of beta-catenin with the transcription factor LEF-1 |journal=Nature |volume=382 |issue= 6592 |pages= 638–42 |year= 1996 |pmid= 8757136 |doi= 10.1038/382638a0 }}
- {{cite journal |vauthors=Bagga R, Emerson BM |title=An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro |journal=Genes Dev. |volume=11 |issue= 5 |pages= 629–39 |year= 1997 |pmid= 9119227 |doi=10.1101/gad.11.5.629 }}
- {{cite journal |vauthors=Bruhn L, Munnerlyn A, Grosschedl R |title=ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function |journal=Genes Dev. |volume=11 |issue= 5 |pages= 640–53 |year= 1997 |pmid= 9119228 |doi=10.1101/gad.11.5.640 }}
- {{cite journal |vauthors=Brannon M, Gomperts M, Sumoy L, etal |title=A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus |journal=Genes Dev. |volume=11 |issue= 18 |pages= 2359–70 |year= 1997 |pmid= 9308964 |doi=10.1101/gad.11.18.2359 | pmc=316518 }}
- {{cite journal |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
- {{cite journal |vauthors=Korinek V, Barker N, Willert K, etal |title=Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse |journal=Mol. Cell. Biol. |volume=18 |issue= 3 |pages= 1248–56 |year= 1998 |pmid= 9488439 |doi= 10.1128/MCB.18.3.1248| pmc=108837 }}
- {{cite journal |vauthors=Prieve MG, Guttridge KL, Munguia J, Waterman ML |title=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 |journal=Mol. Cell. Biol. |volume=18 |issue= 8 |pages= 4819–32 |year= 1998 |pmid= 9671491 |doi= 10.1128/MCB.18.8.4819| pmc=109067 }}
- {{cite journal |vauthors=Levanon D, Goldstein RE, Bernstein Y, etal |title=Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 20 |pages= 11590–5 |year= 1998 |pmid= 9751710 |doi=10.1073/pnas.95.20.11590 | pmc=21685 }}
- {{cite journal |vauthors=Hovanes K, Li TW, Waterman ML |title=The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing |journal=Nucleic Acids Res. |volume=28 |issue= 9 |pages= 1994–2003 |year= 2000 |pmid= 10756202 |doi=10.1093/nar/28.9.1994 | pmc=103301 }}
- {{cite journal |vauthors=Labbé E, Letamendia A, Attisano L |title=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 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 15 |pages= 8358–63 |year= 2000 |pmid= 10890911 |doi= 10.1073/pnas.150152697 | pmc=26952 }}
- {{cite journal |vauthors=Brantjes H, Roose J, van De Wetering M, Clevers H |title=All Tcf HMG box transcription factors interact with Groucho-related co-repressors |journal=Nucleic Acids Res. |volume=29 |issue= 7 |pages= 1410–9 |year= 2001 |pmid= 11266540 |doi=10.1093/nar/29.7.1410 | pmc=31284 }}
{{Refend}} External links - {{MeshName|LEF1+protein,+human}}
{{NLM content}}{{PDB Gallery|geneid=51176}}{{Transcription factors|g4}} 1 : Transcription factors |