LEF1_HUMAN
Domain
Proline-rich and acidic regions are implicated in the activation functions of RNA polymerase II transcription factors.
Function
Transcription factor that binds DNA in a sequence-specific manner (PubMed:2010090). Participates in the Wnt signaling pathway (By similarity). Activates transcription of target genes in the presence of CTNNB1 and EP300 (By similarity). PIAG antagonizes both Wnt-dependent and Wnt-independent activation by LEF1 (By similarity). TLE1, TLE2, TLE3 and TLE4 repress transactivation mediated by LEF1 and CTNNB1 (PubMed:11266540). Regulates T-cell receptor alpha enhancer function (PubMed:19653274). Required for IL17A expressing gamma-delta T-cell maturation and development, via binding to regulator loci of BLK to modulate expression (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity). May play a role in hair cell differentiation and follicle morphogenesis (By similarity).
Isoform 1
Transcriptionally activates MYC and CCND1 expression and enhances proliferation of pancreatic tumor cells.
Isoform 3
Lacks the CTNNB1 interaction domain and may therefore be an antagonist for Wnt signaling.
Isoform 5
Transcriptionally activates the fibronectin promoter, binds to and represses transcription from the E-cadherin promoter in a CTNNB1-independent manner, and is involved in reducing cellular aggregation and increasing cell migration of pancreatic cancer cells.
Post-translational modifications
Phosphorylated at Thr-155 and/or Ser-166 by NLK. Phosphorylation by NLK at these sites represses LEF1-mediated transcriptional activation of target genes of the canonical Wnt signaling pathway.
Sequence Similarities
Belongs to the TCF/LEF family.
Tissue Specificity
Detected in thymus. Not detected in normal colon, but highly expressed in colon cancer biopsies and colon cancer cell lines. Expressed in several pancreatic tumors and weakly expressed in normal pancreatic tissue. Isoforms 1 and 5 are detected in several pancreatic cell lines.
Cellular localization
- Nucleus
- Found in nuclear bodies upon PIASG binding.
Alternative names
Lymphoid enhancer-binding factor 1, LEF-1, T cell-specific transcription factor 1-alpha, TCF1-alpha, LEF1