Lymphoid enhancer-binding factor 1

LEF1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2LEF, 3OUW, 3OUX
Identifiers
Aliases	LEF1, LEF-1, TCF10, TCF1ALPHA, TCF7L3, lymphoid enhancer binding factor 1
External IDs	MGI: 96770 HomoloGene: 7813 GeneCards: LEF1
Gene location (Human)
Chr.	Chromosome 4 (human)[1]
End	108,168,956 bp[1]
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)[2]
End	131,224,356 bp[2]
RNA expression pattern
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	• GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • histone deacetylase binding; • armadillo repeat domain binding; • estrogen receptor binding; • RNA polymerase II regulatory region sequence-specific DNA binding; • transcription factor binding; • estrogen receptor activity; • gamma-catenin binding; • histone binding; • C2H2 zinc finger domain binding; • chromatin binding; • cysteine-type endopeptidase inhibitor activity involved in apoptotic process; • GO:0001948 protein binding; • DNA binding, bending; • DNA binding; • sequence-specific DNA binding; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • beta-catenin binding; • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	• cytoplasm; • cell nucleus; • transcription regulator complex; • beta-catenin-TCF complex; • nucleoplasm; • protein-DNA complex;
Biological process	• somitogenesis; • tongue development; • paraxial mesoderm formation; • regulation of transcription from RNA polymerase II promoter; • negative regulation of DNA binding; • T cell receptor V(D)J recombination; • transcription from RNA polymerase II promoter; • cellular response to cytokine stimulus; • mammary gland development; • negative regulation of interleukin-13 production; • odontogenesis of dentin-containing tooth; • muscle fiber development; • apoptotic process involved in blood vessel morphogenesis; • cell chemotaxis; • negative regulation of canonical Wnt signaling pathway; • face morphogenesis; • neutrophil differentiation; • negative regulation of interleukin-5 production; • regulation of transcription, DNA-templated; • dentate gyrus development; • apoptotic process involved in morphogenesis; • transcription, DNA-templated; • positive regulation of transcription, DNA-templated; • positive regulation of cell growth; • regulation of Wnt signaling pathway; • embryonic limb morphogenesis; • hypothalamus development; • branching involved in blood vessel morphogenesis; • trachea gland development; • regulation of striated muscle tissue development; • positive regulation of cell-cell adhesion; • forebrain neuroblast division; • eye pigmentation; • negative regulation of apoptotic process; • sprouting angiogenesis; • negative regulation of transcription from RNA polymerase II promoter; • positive regulation of epithelial to mesenchymal transition; • BMP signaling pathway; • positive regulation of cell cycle process; • osteoblast differentiation; • histone H3 acetylation; • formation of radial glial scaffolds; • positive regulation of granulocyte differentiation; • alpha-beta T cell differentiation; • canonical Wnt signaling pathway; • negative regulation of transcription, DNA-templated; • sensory perception of taste; • cellular response to interleukin-4; • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; • cell development; • negative regulation of cell-cell adhesion; • negative regulation of interleukin-4 production; • negative regulation of striated muscle tissue development; • positive regulation of cell migration; • Wnt signaling pathway; • T-helper 1 cell differentiation; • positive regulation of cell proliferation in bone marrow; • anatomical structure regression; • chorio-allantoic fusion; • negative regulation of apoptotic process in bone marrow; • B cell proliferation; • positive regulation of gene expression; • vasculature development; • forebrain radial glial cell differentiation; • neural crest cell migration; • positive regulation of cell proliferation; • forebrain neuron differentiation; • histone H4 acetylation; • hippocampus development; • negative regulation of estrogen receptor binding; • positive regulation of transcription from RNA polymerase II promoter; • Wnt signaling pathway, calcium modulating pathway; • steroid hormone mediated signaling pathway; • odontoblast differentiation; • beta-catenin-TCF complex assembly; • epithelial–mesenchymal transition; • regulation of cell-cell adhesion; • secondary palate development;
	Sources:Amigo / QuickGO
Orthologs
	51176
	16842
	ENSG00000138795
	ENSMUSG00000027985
	Q9UJU2; Q659G9
	P27782
	NM_001130713; NM_001130714; NM_001166119; NM_016269
NM_001276402; NM_001276403; NM_010703; NM_001379059; NM_001379060;
	NM_001379061; NM_001379062
	NP_001124185; NP_001124186; NP_001159591; NP_057353; NP_057353.1
NP_001263331; NP_001263332; NP_034833; NP_001365988; NP_001365989;
	NP_001365990; NP_001365991
	Wikidata
View/Edit Human	View/Edit Mouse

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

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

GRCh38: Ensembl release 89: ENSG00000138795 - Ensembl, May 2017
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 (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.
"Entrez Gene: LEF1 lymphoid enhancer-binding factor 1".
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.
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.
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.
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.
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.
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.
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.
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. S2CID 4369341.
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.
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.
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.
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.

External links

LEF1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000138795 - Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid1783375-5] 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.

[entrez-6] "Entrez Gene: LEF1 lymphoid enhancer-binding factor 1".

[Erdfelder_et_al.-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.

[Eskandari_et.al-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.

[pmid20360943-9] 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.

[pmid11696550-10] 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.

[pmid10617663-11] 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.

[pmid15684397-12] 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.

[pmid12748295-13] 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.

[pmid8757136-14] 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. S2CID 4369341.

[pmid10890911-15] 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". Proc. Natl. Acad. Sci. U.S.A. 97 (15): 8358–63. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911.

[pmid12446687-16] 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.

[pmid12032083-17] 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.

[pmid11731474-18] 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.