Lymphoid enhancer-binding factor 1

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Lymphoid enhancer-binding factor 1
Protein LEF1 PDB 2lef.png
PDB rendering based on 2lef.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols LEF1 ; LEF-1; TCF10; TCF1ALPHA; TCF7L3
External IDs OMIM153245 MGI96770 HomoloGene7813 GeneCards: LEF1 Gene
RNA expression pattern
PBB GE LEF1 221558 s at tn.png
PBB GE LEF1 210948 s at tn.png
PBB GE LEF1 221557 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 51176 16842
Ensembl ENSG00000138795 ENSMUSG00000027985
UniProt Q9UJU2 P27782
RefSeq (mRNA) NM_001130713 NM_001276402
RefSeq (protein) NP_001124185 NP_001263331
Location (UCSC) Chr 4:
108.97 – 109.09 Mb
Chr 3:
131.11 – 131.22 Mb
PubMed search [1] [2]

Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene.[1]

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).[2]

Clinical significance[edit]

LEF1 is highly overexpressed and associated with disease progression and poor prognosis in B-cell chronic lymphocytic leukemia.[3] It is also a promising potential drug target.[4]

Interactions[edit]

Lymphoid enhancer-binding factor 1 has been shown to interact with:

References[edit]

  1. ^ Milatovich A, Travis A, Grosschedl R, Francke U (Mar 1992). "Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf". Genomics 11 (4): 1040–8. doi:10.1016/0888-7543(91)90030-I. PMID 1783375. 
  2. ^ "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1". 
  3. ^ Erdfelder F, Hertweck M, Filipovich A,Uhrmacher S, Kreuzer KA (2010). "High lymphoid enhancer- binding factor-1 expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia". Hematology Reports 2 (1). doi:10.4081/hr.2010.e3. 
  4. ^ Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlösser A, Schmitt EK, Hallek M, Kreuzer KA (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): 326–35. PMC 2847740. PMID 20360943. 
  5. ^ Boras K, Hamel PA (January 2002). "Alx4 binding to LEF-1 regulates N-CAM promoter activity". J. Biol. Chem. 277 (2): 1120–7. doi:10.1074/jbc.M109912200. PMID 11696550. 
  6. ^ 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". J. Biol. Chem. 275 (1): 651–6. doi:10.1074/jbc.275.1.651. PMID 10617663. 
  7. ^ 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". Mol. Cell. Biol. 25 (4): 1475–88. doi:10.1128/MCB.25.4.1475-1488.2005. PMC 548008. PMID 15684397. 
  8. ^ 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". Mol. Cell. Biol. 23 (11): 3936–50. doi:10.1128/MCB.23.11.3936-3950.2003. PMC 155208. PMID 12748295. 
  9. ^ 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): 638–42. doi:10.1038/382638a0. PMID 8757136. 
  10. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 97 (15): 8358–63. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911. 
  11. ^ 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". J. Biol. Chem. 278 (6): 3776–85. doi:10.1074/jbc.M210081200. PMID 12446687. 
  12. ^ 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". EMBO J. 21 (11): 2703–14. doi:10.1093/emboj/21.11.2703. PMC 126018. PMID 12032083. 
  13. ^ 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 Dev. 15 (23): 3088–103. doi:10.1101/gad.944801. PMC 312834. PMID 11731474. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.