関: LEF1

WordNet

be a contributing factor; "make things factor into a companys profitability"
any of the numbers (or symbols) that form a product when multiplied together
an independent variable in statistics
anything that contributes causally to a result; "a number of factors determined the outcome"
consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
executed with proper legal authority; "a binding contract"
the protective covering on the front, back, and spine of a book; "the book had a leather binding" (同)book binding, cover, back
strip sewn over or along an edge for reinforcement or decoration
the capacity to attract and hold something
an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
a concept whose truth can be proved; "scientific hypotheses are not facts"
a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
increase; "This will enhance your enjoyment"; "heighten the tension" (同)heighten, raise
make better or more attractive; "This sauce will enhance the flavor of the meat"
resembling lymph or lymphatic tissues

PrepTutorEJDIC

(…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
義務的な,拘束力ある / 〈U〉しばること;〈C〉しばる物 / 〈C〉製本,装丁 / 〈U〉縁(‘ふち')取り材料
〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
…‘の'程度(仮値など)を高める
リンパ状(液)の

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/24 04:00:02」(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.

UpToDate Contents

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1. 成人における骨髄異形成症候群の予後 prognosis of the myelodysplastic syndromes in adults
2. 先天性好中球減少症 congenital neutropenia

English Journal

Bmp7 and lef1 are the downstream effectors of androgen signaling in androgen-induced sex characteristics development in medaka.

Ogino Y, Hirakawa I, Inohaya K, Sumiya E, Miyagawa S, Denslow N, Yamada G, Tatarazako N, Iguchi T.Author information Okazaki Institute for Integrative Bioscience (Y.O., I.H., E.S., S.M., T.I.), National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology (Y.O., I.H., E.S., S.M., T.I.), Faculty of Life Science, The Graduate University for Advanced Studies, Aichi 444-8787, Japan; Department of Biological Information (K.I.), Tokyo Institute of Technology, Yokohama 226-8501, Japan; Department of Physiological Sciences (N.D.), Center for Environmental and Human Toxicology, University of Florida, Gainesville, Florida 32611; Department of Developmental Genetics (G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; and National Institute for Environmental Studies (N.T.), Ibaraki, 305-8506, Japan.AbstractAndrogens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual character for appendage development, the formation of papillary processes in the anal fin, which has been induced in females by exogenous androgen exposure. This current study shows that the development of papillary processes is promoted by androgen-dependent augmentation of bone morphogenic protein 7 (Bmp7) and lymphoid enhancer-binding factor-1 (Lef1). Androgen receptor (AR) subtypes, ARα and ARβ, are expressed in the distal region of outgrowing bone nodules of developing papillary processes. Development of papillary processes concomitant with the induction of Bmp7 and Lef1 in the distal bone nodules by exposure to methyltestosterone was significantly suppressed by an antiandrogen, flutamide, in female medaka. When Bmp signaling was inhibited in methyltestosterone-exposed females by its inhibitor, dorsomorphin, Lef1 expression was suppressed accompanied by reduced proliferation in the distal bone nodules and retarded bone deposition. These observations indicate that androgen-dependent expressions of Bmp7 and Lef1 are required for the bone nodule outgrowth leading to the formation of these secondary sex characteristics in medaka. The formation of androgen-induced papillary processes may provide insights into the mechanisms regulating the specification of sexual features in vertebrates.
Endocrinology.Endocrinology.2014 Feb;155(2):449-62. doi: 10.1210/en.2013-1507. Epub 2013 Nov 18.
Androgens play key roles in the morphological specification of male type sex attractive and reproductive organs, whereas little is known about the developmental mechanisms of such secondary sex characters. Medaka offers a clue about sexual differentiation. They show a prominent masculine sexual char
PMID 24248458

Buffalo alpha S1-casein gene 5'-flanking region and its interspecies comparison.

Patel AK, Singh M, Suryanarayana VV.Author information Department of Animal Biotechnology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, India.AbstractThe expression of milk protein genes is tightly regulated in a spatio-temporal manner through the combinatorial interaction of lactogenic hormones and a set of transcription factors mediating developmental and tissue-specific gene expression. The recruitment of a unique set of transcription factors is determined by the cis-regulatory motifs present in the gene promoter region. Here, we report the isolation, sequencing, structural analysis and interspecies comparison of the 5'cis-regulatory region of the buffalo alpha S1 (αS1)-casein gene. The proximal promoter region of the buffalo αS1-casein gene harbored the insertion of a 72-bp fragment of long interspersed nuclear element of the L1_BT retrotransposon family. Among the core and vertebrate-specific promoter elements, the motifs for the binding of Brn POU domain factors (BRNF), Lim homeodomain factors (LHXF), NK6 homeobox transcription factors (NKX6), nuclear factor kappa B/c-rel (NFKB), AT-rich interactive domain factor (ARID), Brn POU domain factor 5 (BRN5), pancreatic and intestinal homeodomain transcription factor (PDX1), Distal-less homeodomain transcription factors (DLXF), T-cell factor/lymphoid enhancer-binding factor-1 (LEFF) and GHF-1 pituitary-specific POU domain transcription factor (PIT1) were over-represented in the αS1-casein gene regulatory region (Z score >4.0). The Multiple EM for Motif elicitation predicted three motifs which consisted of the sequences known to bind mammary gland factor/signal transducer and activator of transcription 5 (MGF/STAT5), estrogen receptor-related alpha (ERα), steroidogenic factor 1 (SF1) and glucocorticoid receptor (GR), indicating their potential role in the mammary gland-specific gene expression. The interspecies comparison of the proximal promoter region revealed conserved sequences for TATA boxes and MGF/STAT5 in all species, whereas activator protein 1 (AP1), pregnancy-specific mammary nuclear factor (PMF), CCAAT/enhancer binding protein (C/EBP), double-stranded and single-stranded DNA-binding protein 1 (DS1 and SS), ying and yang factor 1 (YY1), and GR half-sites were among ruminants. The functional significance of the L1_BT retrotransposon insertion on the buffalo αS1-casein gene expression needs to be experimentally validated.
Journal of applied genetics.J Appl Genet.2014 Feb;55(1):75-87. doi: 10.1007/s13353-013-0176-7. Epub 2013 Oct 19.
The expression of milk protein genes is tightly regulated in a spatio-temporal manner through the combinatorial interaction of lactogenic hormones and a set of transcription factors mediating developmental and tissue-specific gene expression. The recruitment of a unique set of transcription factors
PMID 24142689

Clinical significance of lymphoid enhancer-binding factor 1 expression in acute myeloid leukemia.

Fu Y, Zhu H, Wu W, Xu J, Chen T, Xu B, Qian S, Li J, Liu P.Author information Department of Hematology.AbstractAbstract Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of the Wnt/β-catenin signaling pathway and its dysregulation is associated with a number of malignant diseases such as leukemia. We explored the expression profile of LEF1 in acute myeloid leukemia (AML) and determined its specific prognostic significance in this disease. The LEF1 mRNA level in patients with previously untreated AML was significantly higher than in normal controls. Patients with AML with relatively higher LEF1 expression were more likely to achieve a complete remission (CR) following induction therapy in comparison to those with a lower LEF1 level. Moreover, we provide the first evidence that primary AML samples with AML1-ETO or PML-RARα have a higher LEF1 level compared with those without each fusion gene. High LEF1 expression predicts a significantly better overall survival for patients with intermediate-risk cytogenetics. High LEF1 level was associated with a favorable relapse-free survival in patients with FLT3-ITD wild-type. Finally, a scoring system based on LEF1 level and mutation status of FLT3-ITD or NPM1 is reliable to predict the outcome for AML with intermediate-risk cytogenetics. Our results indicate that LEF1 contributes to the pathophysiology of AML and could serve as a novel predictor of better treatment response. LEF1 level may be incorporated into an improved risk classification system for certain specific subtypes of AML.
Leukemia & lymphoma.Leuk Lymphoma.2014 Feb;55(2):371-7. doi: 10.3109/10428194.2013.805759. Epub 2013 Jul 8.
Abstract Lymphoid enhancer-binding factor 1 (LEF1) is a downstream effector of the Wnt/β-catenin signaling pathway and its dysregulation is associated with a number of malignant diseases such as leukemia. We explored the expression profile of LEF1 in acute myeloid leukemia (AML) and determined its
PMID 23713453

Japanese Journal

Intestinal Peyer's patches prevent tumorigenesis in ApcMin/+ mice

Fujimoto Kyoko,Fujii Gen,Sakurai Hitomi,Yoshitome Hiroko,Mutoh Michihiro,Wada Morimasa
Journal of Clinical Biochemistry and Nutrition, 2015
… Increasing the number of Peyer's patches decreased interleukin-17 production, which showed a dose dependent correlation with transcription factor/lymphoid enhancer-binding factor. …
NAID 130004704978

Immunolocalization of SP6, LEF1 and Associated Factors in the Tooth Germ of Rat Molars

Moriguchi Mitsuko,Kosika Mayu,Miake Yasuo,Yamaguchi Yasuaki,Yamazaki Takaki,Yamamoto Hitoshi
Journal of Hard Tissue Biology 22(4), 481-488, 2013
… Lymphoid enhancer-binding factor 1 (LEF1) is a transcription factor in the Wnt/β-catenin signaling pathway. … Specificity Protein 6/Epiprofin (SP6) is a transcription factor that mediates the signaling pathway between bone morphogenetic protein (BMP) and the Wnt/β-catenin. …
NAID 130004480620

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

LABBE E
Proc Natl Acad Sci USA 97(15), 8358-8363, 2000
NAID 80011893073

「LEF1」

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 transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription; • DNA binding; • chromatin binding; • sequence-specific DNA binding transcription factor activity; • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; • 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; • epithelial to mesenchymal transition; • sprouting angiogenesis; • transcription from RNA polymerase II promoter; • positive regulation of cell proliferation; • 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; • 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; • 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; • 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
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