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lymphoid enhancer-binding factor 1; LEF-1; T cell-specific transcription factor 1-alpha; TCF1-alpha (LEF1)

Function: - role in the Wnt signaling pathway - binds to: a) smads, selectively inhibits tgf responsive genes [3] b) beta-catenin - regulated by wnt1/beta-catenin signaling - regulated by wnt3/beta-catenin signaling - role in induction of: cyclin D1, myc, TCF-1, PPAR-gamma, MMP-7, axin-2, CD44 - activates transcription of target genes in the presence of CTNNB1 & EP300 - may play a role in hair cell differentiation & follicle morphogenesis - TLE1, TLE2, TLE3 & TLE4 repress transactivation mediated by LEF1 & CTNNB1 - regulates T-cell receptor alpha enhancer function - binds DNA in a sequence-specific manner - PIAG antagonizes both Wnt-dependent & Wnt-independent activation by LEF1 (putative) - isoform 3 lacks the CTNNB1 interaction domain & may be an antagonist for Wnt signaling - binds the armadillo repeat of CTNNB1 & forms a stable complex - interacts with EP300, TLE1 & PIASG (putative) - binds THOC4, MDFI & MDFIC - microphthalmia-associated transcription factor [2] Structure: - proline-rich & acidic regions are implicated in the activation functions of RNA polymerase 2 transcription factors - belongs to the TCF/LEF family - contains 1 HMG box DNA-binding domain - HMG box binds to A[TA]TCAAAG present in many T-cell enhancers Compartment: - nucleus (putative) - found in nuclear bodies upon PIASG binding (putative) Alternative splicing: - named isoforms=4 - additional isoforms seem to exist Alternative promoter usage: Expression: - expression is complex & overlapping during embryogenesis - detected in thymus - not detected in normal colon Pathology: - highly expressed in colon cancer biopsies & colon cancer cell lines - loss of expression seen in a subset of peripheral T-cell lymphomas - LEF1 gene disruption does not affect T lineage, but has striking effects on tooth, hair follicle & mammary gland development & on the trigeminal nucleus in the brain

Related

Wnt-1 signalling

General

DNA-binding protein transcription factor (TF)

Properties

SIZE: entity length = 399 aa MW = 44 kD COMPARTMENT: cell nucleus MOTIF: binding site SITE: 1-62 FOR-BINDING-OF: beta catenin MOTIF: glycine-rich region {6-13} acidic region {14-52} MOTIF: acidic residue (SEVERAL) proline-rich region SITE: 77-273 MOTIF: proline residue (SEVERAL) HMG box SITE: 299-367 lysine-rich region {374-379} MOTIF: lysine residue (SEVERAL)

Database Correlations

OMIM 153245 UniProt Q9UJU2 PFAM correlations Entrez Gene 51176 Kegg hsa:5117

References

  1. Verbeek S, Izon D, Hofhuis F, Robanus-Maandag E, te Riele H, van de Wetering M, Oosterwegel M, Wilson A, MacDonald HR, Clevers H. An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature. 1995 Mar 2;374(6517):70-4. PMID: 7870176
  2. Yasumoto et al. EMBO J. 21(11):2703-1, 2002 PMID: 12032083
  3. Cui et al. Oncogene 24(24):3864-74, 2005 PMID: 15750622