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. © 2011 Macmillan Publishers Limited All rights reserved.