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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/28 20:44:00」(JST)

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

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).^[2]

Clinical significance

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

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

ALX4,^[5]
AML-1,^[6]
CTNNB1,^[7]^[8]^[9]^[10]
EP300,^[11]
MITF^[12]
PIAS4,^[13]
SMAD2,^[10] and
SMAD3.^[10]

References

^ 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). doi:10.4081/hr.2010.e3.
^ 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.
^ 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.
^ ^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.
^ 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 on a gene on human chromosome 4 is a stub. You can help Wikipedia by expanding it.

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English Journal

Expression of LEF1 in mantle cell lymphoma.

O'Malley DP1, Lee JP2, Bellizzi AM3.
Annals of diagnostic pathology.Ann Diagn Pathol.2017 Feb;26:57-59. doi: 10.1016/j.anndiagpath.2016.09.016. Epub 2016 Nov 22.
Small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL) and mantle cell lymphoma (MCL) usually are distinctly different in regard to clinical presentation, morphology, immunophenotype and molecular/genetic findings. In spite of this, select cases may show overlapping characteristics and re
PMID 28038713

TCF7L2 mediates the cellular and behavioral response to chronic lithium treatment in animal models.

Misztal K1, Brozko N2, Nagalski A3, Szewczyk LM4, Krolak M5, Brzozowska K2, Kuznicki J1, Wisniewska MB6.
Neuropharmacology.Neuropharmacology.2017 Feb;113(Pt A):490-501. doi: 10.1016/j.neuropharm.2016.10.027. Epub 2016 Oct 25.
The mechanism of lithium's therapeutic action remains obscure, hindering the discovery of safer treatments for bipolar disorder. Lithium can act as an inhibitor of the kinase GSK3α/β, which in turn negatively regulates β-catenin, a co-activator of LEF1/TCF transcription factors. However, unclear
PMID 27793772

Activation of EVI1 transcription by the LEF1/β-catenin complex with p53-alteration in myeloid blast crisis of chronic myeloid leukemia.

Manachai N1, Saito Y1, Nakahata S1, Bahirvani AG2, Osato M2, Morishita K3.
Biochemical and biophysical research communications.Biochem Biophys Res Commun.2017 Jan 22;482(4):994-1000. doi: 10.1016/j.bbrc.2016.11.146. Epub 2016 Nov 28.
The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to pr
PMID 27908728

Japanese Journal

R26-WntVis reporter mice showing graded response to Wnt signal levels

Genes to Cells 21(6), 661-669, 2016-03-31
NAID 120006306641

Regulation of the TMEPAI promoter by TCF7L2 : the C-terminal tail of TCF7L2 is essential to activate the TMEPAI gene

The journal of biochemistry 159(1), 27-30, 2016-01
NAID 120005716427

バイオマーカーとしてのmiRNA －薬の副作用を中心として－

日本毒性学会学術年会 43.1(0), S12-6, 2016
NAID 130005260944

Related Pictures

CST - LEF1 (C18A7) Rabbit mAb | Combinatorial expression of Lef1 LEF1 antibody 抗体】武汉其它 Graphical representation of LEF1.com LEF1 Antibody - Bethyl Laboratories LEF1 (C12A5) Rabbit mAb #2230 | CST 抗体 β-Catenin&LEF1 transactivates the Lef1 RNA in situ Gene Expression Assay

★リンクテーブル★

リンク元	「lymphoid enhancer-binding factor 1」「リンパ系エンハンサー結合因子1」
関連記事	「LE」

「lymphoid enhancer-binding factor 1」

Lymphoid enhancer-binding factor 1
	PDB rendering based on 2lef.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2lef
Identifiers
Symbols	LEF1 ; LEF-1; TCF10; TCF1ALPHA; TCF7L3
External IDs	OMIM: 153245 MGI: 96770 HomoloGene: 7813 GeneCards: LEF1 Gene
Gene ontology
Molecular function	• RNA polymerase II regulatory region sequence-specific DNA binding; • RNA polymerase II core promoter proximal region sequence-specific DNA binding; • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; • DNA binding; • chromatin binding; • transcription factor activity, sequence-specific DNA binding; • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; • protein binding; • beta-catenin binding; • transcription factor binding; • DNA binding, bending; • estrogen receptor activity; • estrogen receptor binding; • enhancer binding; • histone binding; • cysteine-type endopeptidase inhibitor activity involved in apoptotic process; • sequence-specific DNA binding; • transcription regulatory region DNA binding; • gamma-catenin binding; • armadillo repeat domain binding; • C2H2 zinc finger domain binding;
Cellular component	• nucleus; • nucleoplasm; • transcription factor complex; • cytoplasm; • protein-DNA complex;
Biological process	• negative regulation of transcription from RNA polymerase II promoter; • patterning of blood vessels; • osteoblast differentiation; • neural crest cell migration; • somitogenesis; • kidney development; • epithelial to mesenchymal transition; • sprouting angiogenesis; • transcription from RNA polymerase II promoter; • positive regulation of cell proliferation; • response to lithium ion; • positive regulation of gene expression; • positive regulation of epithelial to mesenchymal transition; • Wnt signaling pathway; • regulation of striated muscle tissue development; • dentate gyrus development; • hypothalamus development; • forebrain radial glial cell differentiation; • forebrain neuroblast division; • forebrain neuron differentiation; • formation of radial glial scaffolds; • regulation of cell-cell adhesion; • negative regulation of cell-cell adhesion; • positive regulation of cell-cell adhesion; • neutrophil differentiation; • positive regulation of cell growth; • embryonic limb morphogenesis; • positive regulation of cell migration; • BMP signaling pathway; • positive regulation of granulocyte differentiation; • mammary gland development; • organ regeneration; • negative regulation of interleukin-13 production; • negative regulation of interleukin-4 production; • negative regulation of interleukin-5 production; • T cell receptor V(D)J recombination; • B cell proliferation; • odontogenesis of dentin-containing tooth; • negative regulation of apoptotic process; • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; • negative regulation of DNA binding; • steroid hormone mediated signaling pathway; • tongue development; • skin development; • positive regulation by host of viral transcription; • histone H3 acetylation; • histone H4 acetylation; • T-helper 1 cell differentiation; • negative regulation of striated muscle tissue development; • negative regulation of transcription, DNA-templated; • positive regulation of transcription, DNA-templated; • positive regulation of transcription from RNA polymerase II promoter; • alpha-beta T cell differentiation; • eye pigmentation; • paraxial mesoderm formation; • generation of neurons; • muscle fiber development; • sensory perception of taste; • palate development; • anatomical structure regression; • canonical Wnt signaling pathway; • face morphogenesis; • cell chemotaxis; • apoptotic process involved in morphogenesis; • chorio-allantoic fusion; • trachea gland development; • cellular response to cytokine stimulus; • cellular response to interleukin-4; • positive regulation of cell proliferation in bone marrow; • negative regulation of apoptotic process in bone marrow; • odontoblast differentiation; • negative regulation of estrogen receptor binding; • positive regulation of cell cycle process; • negative regulation of canonical Wnt signaling pathway; • apoptotic process involved in patterning of blood vessels;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;