Lymphoid enhancer-binding factor 1

Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene.[5] It's a member of T cell factor/lymphoid enhancer factor (TCF/LEF) family.

LEF1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesLEF1, LEF-1, TCF10, TCF1ALPHA, TCF7L3, lymphoid enhancer binding factor 1
External IDsMGI: 96770 HomoloGene: 7813 GeneCards: LEF1
Orthologs
SpeciesHumanMouse
Entrez

51176

16842

Ensembl

ENSG00000138795

ENSMUSG00000027985

UniProt

Q9UJU2
Q659G9

P27782

RefSeq (mRNA)

NM_001130713
NM_001130714
NM_001166119
NM_016269

RefSeq (protein)

NP_001124185
NP_001124186
NP_001159591
NP_057353
NP_057353.1

Location (UCSC)Chr 4: 108.05 – 108.17 MbChr 3: 130.9 – 131.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

  1. GRCh38: Ensembl release 89: ENSG00000138795 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000027985 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 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.
  6. "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1".
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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. doi:10.1038/382638a0. PMID 8757136. S2CID 4369341.
  15. 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. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911.
  16. Barolo S, Posakony JW (May 2002). "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. 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).
  17. 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.
  18. 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.
  19. 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

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