Lymphoid enhancer-binding factor 1

Protein-coding gene in the species Homo sapiens
LEF1
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2LEF, 3OUW, 3OUX

Identifiers
AliasesLEF1, LEF-1, TCF10, TCF1ALPHA, TCF7L3, lymphoid enhancer binding factor 1
External IDsMGI: 96770; HomoloGene: 7813; GeneCards: LEF1; OMA:LEF1 - orthologs
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]
Gene location (Mouse)
Chromosome 3 (mouse)
Chr.Chromosome 3 (mouse)[2]
Chromosome 3 (mouse)
Genomic location for LEF1
Genomic location for LEF1
Band3 G3|3 60.78 cMStart130,904,120 bp[2]
End131,018,005 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • thymus

  • lymph node

  • tibia

  • oocyte

  • lateral nuclear group of thalamus

  • secondary oocyte

  • blood

  • appendix

  • buccal mucosa cell

  • granulocyte
Top expressed in
  • tail of embryo

  • genital tubercle

  • thymus

  • lamina propria of urethra

  • mesenteric lymph nodes

  • maxillary prominence

  • tooth germ

  • blood

  • zygote

  • hair follicle
More reference expression data
BioGPS




More reference expression data
Gene ontology
Molecular function
  • DNA-binding transcription factor activity
  • DNA-binding transcription activator activity, RNA polymerase II-specific
  • histone deacetylase binding
  • armadillo repeat domain binding
  • estrogen receptor binding
  • RNA polymerase II transcription 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
  • 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
  • RNA polymerase II cis-regulatory region sequence-specific DNA binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
Cellular component
  • cytoplasm
  • nucleus
  • transcription regulator complex
  • beta-catenin-TCF complex
  • nucleoplasm
  • protein-DNA complex
Biological process
  • somitogenesis
  • tongue development
  • paraxial mesoderm formation
  • regulation of transcription by RNA polymerase II
  • negative regulation of DNA binding
  • T cell receptor V(D)J recombination
  • transcription by RNA polymerase II
  • cellular response to cytokine stimulus
  • mammary gland development
  • negative regulation of interleukin-13 production
  • odontogenesis of dentin-containing tooth
  • 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 by RNA polymerase II
  • 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 cell
  • B cell proliferation
  • positive regulation of gene expression
  • vasculature development
  • forebrain radial glial cell differentiation
  • neural crest cell migration
  • positive regulation of cell population proliferation
  • forebrain neuron differentiation
  • histone H4 acetylation
  • hippocampus development
  • positive regulation of transcription by RNA polymerase II
  • Wnt signaling pathway, calcium modulating pathway
  • steroid hormone mediated signaling pathway
  • odontoblast differentiation
  • beta-catenin-TCF complex assembly
  • epithelial to mesenchymal transition
  • regulation of cell-cell adhesion
  • secondary palate development
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

51176

16842

Ensembl

ENSG00000138795

ENSMUSG00000027985

UniProt

Q9UJU2
Q659G9

P27782

RefSeq (mRNA)

NM_001130713
NM_001130714
NM_001166119
NM_016269

NM_001276402
NM_001276403
NM_010703
NM_001379059
NM_001379060

NM_001379061
NM_001379062

RefSeq (protein)

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

Location (UCSC)Chr 4: 108.05 – 108.17 MbChr 3: 130.9 – 131.02 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] It is a member of T cell factor/lymphoid enhancer factor (TCF/LEF) family.

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

  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:". 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.
  5. ^ Milatovich A, Travis A, Grosschedl R, Francke U (December 1991). "Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23-q25) and mouse chromosome 3 near Egf". Genomics. 11 (4): 1040–1048. 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 (January 2010). "High lymphoid enhancer-binding factor-1 expression is associated with disease progression and poor prognosis in chronic lymphocytic leukemia". Hematology Reports. 2 (1): e3. 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. S2CID 52172531.
  9. ^ Gandhirajan RK, Staib PA, Minke K, Gehrke I, Plickert G, Schlösser A, et al. (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): 326–335. 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". The Journal of Biological Chemistry. 277 (2): 1120–1127. 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". The Journal of Biological Chemistry. 275 (1): 651–656. 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". Molecular and Cellular Biology. 25 (4): 1475–1488. 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". Molecular and Cellular Biology. 23 (11): 3936–3950. 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): 638–642. Bibcode:1996Natur.382..638B. doi:10.1038/382638a0. PMID 8757136. S2CID 4369341.
  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". Proceedings of the National Academy of Sciences of the United States of America. 97 (15): 8358–8363. Bibcode:2000PNAS...97.8358L. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911.
  16. ^ Barolo S, Posakony JW (May 2002). "Three habits of highly effective signaling pathways: principles of transcriptional control by developmental cell signaling". Genes & Development. 16 (10). Cold Spring Harbor Laboratory Press & The Genetics Society: 1167–1181. doi:10.1101/gad.976502. PMID 12023297. S2CID 14376483. p. 1170: In ... zebrafish, reporter transgenes containing the TOPFLASH promoter are expressed in certain Wnt-responsive cell types (...Dorsky et al. 2002).
  17. ^ 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". The Journal of Biological Chemistry. 278 (6): 3776–3785. doi:10.1074/jbc.M210081200. PMID 12446687.
  18. ^ 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". The EMBO Journal. 21 (11): 2703–2714. doi:10.1093/emboj/21.11.2703. PMC 126018. PMID 12032083.
  19. ^ 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 & Development. 15 (23): 3088–3103. doi:10.1101/gad.944801. PMC 312834. PMID 11731474.

Further reading

  • Waterman ML (2004). "Lymphoid enhancer factor/T cell factor expression in colorectal cancer". Cancer and Metastasis Reviews. 23 (1–2): 41–52. doi:10.1023/A:1025858928620. PMID 15000148. S2CID 20996511.
  • Skokowa J, Welte K (June 2007). "LEF-1 is a decisive transcription factor in neutrophil granulopoiesis". Annals of the New York Academy of Sciences. 1106 (1): 143–151. Bibcode:2007NYASA1106..143S. doi:10.1196/annals.1392.012. PMID 17360796. S2CID 30579011.
  • Travis A, Amsterdam A, Belanger C, Grosschedl R (May 1991). "LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]". Genes & Development. 5 (5): 880–894. doi:10.1101/gad.5.5.880. PMID 1827423.
  • van de Wetering M, Oosterwegel M, Dooijes D, Clevers H (January 1991). "Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box". The EMBO Journal. 10 (1): 123–132. doi:10.1002/j.1460-2075.1991.tb07928.x. PMC 452620. PMID 1989880.
  • Waterman ML, Fischer WH, Jones KA (April 1991). "A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer". Genes & Development. 5 (4): 656–669. doi:10.1101/gad.5.4.656. PMID 2010090.
  • Zhou P, Byrne C, Jacobs J, Fuchs E (March 1995). "Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate". Genes & Development. 9 (6): 700–713. doi:10.1101/gad.9.6.700. PMID 7537238.
  • Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Prieve MG, Guttridge KL, Munguia JE, Waterman ML (March 1996). "The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differentially expressed Srp1-nuclear localization sequence receptor proteins". The Journal of Biological Chemistry. 271 (13): 7654–7658. doi:10.1074/jbc.271.13.7654. PMID 8631802.
  • 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): 638–642. Bibcode:1996Natur.382..638B. doi:10.1038/382638a0. PMID 8757136. S2CID 4369341.
  • Bagga R, Emerson BM (March 1997). "An HMG I/Y-containing repressor complex and supercoiled DNA topology are critical for long-range enhancer-dependent transcription in vitro". Genes & Development. 11 (5): 629–639. doi:10.1101/gad.11.5.629. PMID 9119227.
  • Bruhn L, Munnerlyn A, Grosschedl R (March 1997). "ALY, a context-dependent coactivator of LEF-1 and AML-1, is required for TCRalpha enhancer function". Genes & Development. 11 (5): 640–653. doi:10.1101/gad.11.5.640. PMID 9119228.
  • Brannon M, Gomperts M, Sumoy L, Moon RT, Kimelman D (September 1997). "A beta-catenin/XTcf-3 complex binds to the siamois promoter to regulate dorsal axis specification in Xenopus". Genes & Development. 11 (18): 2359–2370. doi:10.1101/gad.11.18.2359. PMC 316518. PMID 9308964.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Korinek V, Barker N, Willert K, Molenaar M, Roose J, Wagenaar G, et al. (March 1998). "Two members of the Tcf family implicated in Wnt/beta-catenin signaling during embryogenesis in the mouse". Molecular and Cellular Biology. 18 (3): 1248–1256. doi:10.1128/MCB.18.3.1248. PMC 108837. PMID 9488439.
  • Prieve MG, Guttridge KL, Munguia J, Waterman ML (August 1998). "Differential importin-alpha recognition and nuclear transport by nuclear localization signals within the high-mobility-group DNA binding domains of lymphoid enhancer factor 1 and T-cell factor 1". Molecular and Cellular Biology. 18 (8): 4819–4832. doi:10.1128/MCB.18.8.4819. PMC 109067. PMID 9671491.
  • Levanon D, Goldstein RE, Bernstein Y, Tang H, Goldenberg D, Stifani S, et al. (September 1998). "Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors". Proceedings of the National Academy of Sciences of the United States of America. 95 (20): 11590–11595. Bibcode:1998PNAS...9511590L. doi:10.1073/pnas.95.20.11590. PMC 21685. PMID 9751710.
  • Hovanes K, Li TW, Waterman ML (May 2000). "The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing". Nucleic Acids Research. 28 (9): 1994–2003. doi:10.1093/nar/28.9.1994. PMC 103301. PMID 10756202.
  • 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". Proceedings of the National Academy of Sciences of the United States of America. 97 (15): 8358–8363. Bibcode:2000PNAS...97.8358L. doi:10.1073/pnas.150152697. PMC 26952. PMID 10890911.
  • Brantjes H, Roose J, van De Wetering M, Clevers H (April 2001). "All Tcf HMG box transcription factors interact with Groucho-related co-repressors". Nucleic Acids Research. 29 (7): 1410–1419. doi:10.1093/nar/29.7.1410. PMC 31284. PMID 11266540.

External links

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

  • v
  • t
  • e
  • 2lef: LEF1 HMG DOMAIN (FROM MOUSE), COMPLEXED WITH DNA (15BP), NMR, 12 STRUCTURES
    2lef: LEF1 HMG DOMAIN (FROM MOUSE), COMPLEXED WITH DNA (15BP), NMR, 12 STRUCTURES
  • v
  • t
  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies