Lymphoid enhancer-binding factor 1

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LEF1
Protein LEF1 PDB 2lef.png
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
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for LEF1
Genomic location for LEF1
Band4q25Start108,047,545 bp[1]
End108,168,956 bp[1]
RNA expression pattern
PBB GE LEF1 210948 s at fs.png

PBB GE LEF1 221557 s at fs.png

PBB GE LEF1 221558 s at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001130713
NM_001130714
NM_001166119
NM_016269

NM_001276402
NM_001276403
NM_010703

RefSeq (protein)

NP_001124185
NP_001124186
NP_001159591
NP_057353
NP_057353.1

NP_001263331
NP_001263332
NP_034833

Location (UCSC)Chr 4: 108.05 – 108.17 MbChr 3: 131.11 – 131.22 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Lymphoid enhancer-binding factor 1 (LEF1) is a protein that in humans is encoded by the LEF1 gene.[5]

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).[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]

Interactions[edit]

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

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138795 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027985 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ 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.
  6. ^ "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1".
  7. ^ 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): 3. 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.
  9. ^ 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. 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". J. Biol. Chem. 277 (2): 1120–7. 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". J. Biol. Chem. 275 (1): 651–6. 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". Mol. Cell. Biol. 25 (4): 1475–88. 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". Mol. Cell. Biol. 23 (11): 3936–50. 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): 638–42. doi:10.1038/382638a0. PMID 8757136.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.