C-terminal-binding Protein Corepresses Epithelial and Proapoptotic Gene Expression Programs

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Apr 5

PMID 12676992

Citations 105

Authors

Madeleine Grooteclaes

Quinn Deveraux

Jeffrey Hildebrand

Qinghong Zhang

Richard H Goodman

Steven M Frisch

Affiliations

Soon will be listed here.

Abstract

The genesis of carcinoma cells often involves epithelial-to-mesenchymal transitions and the acquisition of apoptosis resistance, but it is unclear whether these alterations are controlled coordinately or independently. Our previously reported effects of adenovirus E1a in human tumor cells raised the possibility that the E1a-interacting corepressor protein C-terminal-binding protein (CtBP) might selectively repress epithelial cell adhesion and proapoptotic genes. Here, we report that CtBP-knockout cells were hypersensitive to apoptosis. Correspondingly, microarray analysis of CtBP-knockout vs. CtBP-rescued mouse embryo fibroblasts revealed that many epithelial-specific and proapoptotic genes were indeed regulated by CtBP. Neither the apoptosis nor the repression activities of CtBP required histidine-315, suggesting that the proposed dehydrogenase activity is not essential for CtBP function. The results presented herein establish two functional roles of CtBP: to corepress epithelial genes, thus permitting epithelial-to-mesenchymal transitions, and to modulate the cellular threshold for apoptotic responses.

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