lymphoid enhancer-binding factor 1; LEF-1; T cell-specific transcription factor 1-alpha; TCF1-alpha (LEF1)
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Function
- role in the Wnt signaling pathway
- binds to:
- smads, selectively inhibits tgf responsive genes[3]
- 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
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
More general terms
Additional terms
References
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/7870176
- ↑ 2.0 2.1 Yasumoto et al. EMBO J. 21(11):2703-1, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/12032083
- ↑ 3.0 3.1 Cui et al. Oncogene 24(24):3864-74, 2005 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15750622