title: E2F1 suppresses Wnt/β-catenin activity through transactivation of β-catenin interacting protein ICAT.
abstract: Deregulation of the pRb/E2F or Wnt/β-catenin pathway occurs frequently in human cancers, which is often associated with inappropriate cell proliferation. Although the oncogenic roles of pRb/E2F1 and Wnt/β-catenin pathways have been well studied, the functional interaction between the two pathways has only recently been characterized. In particular, E2F1 has been recently reported to negatively regulate Wnt/β-catenin activity in human colorectal cancers, though the mechanism underlying this regulation is not fully understood. Here we provide evidence that β-catenin interacting protein 1 (CTNNBIP1), also known as ICAT (inhibitor of β-catenin and TCF4), functions as a crucial node to mediate the cross talk between E2F1 and β-catenin signaling. We show that ICAT is a direct transcriptional target of E2F1, and that activation of ICAT by E2F1 is required for E2F1 to inhibit β-catenin activity. This study provides a mechanistic insight into the antagonistic interaction between E2F1 and β-catenin signaling.
authors.affiliation: Department of Cancer Biology and Pharmacology, Genome Institute of Singapore, A*Star (Agency for Science, Technology and Research), Biopolis, Singapore.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Zheng
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Tan
authors.forename: Q
authors.initials: Q
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D045744:Cell Line, Tumor; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C411982:CTNNBIP1 protein, human; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051176:beta Catenin