From Wikipedia, the free encyclopedia
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.
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:
References
^
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
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
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