C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs

Madeleine Grooteclaes, Quinn Deveraux, Jeffrey Hildebrand, Qinghong Zhang, Richard Goodman, Steven M. Frisch

Research output: Contribution to journalArticle

140 Citations (Scopus)

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 core-press epithelial genes, thus permitting epithelial-to-mesenchymal transitions, and to modulate the cellular threshold for apoptotic responses.

Original languageEnglish (US)
Pages (from-to)4568-4573
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number8
DOIs
StatePublished - Apr 15 2003

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Gene Expression
Epithelial-Mesenchymal Transition
Apoptosis
Genes
Co-Repressor Proteins
C-terminal binding protein
Microarray Analysis
Protein C
Histidine
Adenoviridae
Cell Adhesion
Oxidoreductases
Embryonic Structures
Fibroblasts
Epithelial Cells
Carcinoma
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. / Grooteclaes, Madeleine; Deveraux, Quinn; Hildebrand, Jeffrey; Zhang, Qinghong; Goodman, Richard; Frisch, Steven M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 8, 15.04.2003, p. 4568-4573.

Research output: Contribution to journalArticle

Grooteclaes, Madeleine ; Deveraux, Quinn ; Hildebrand, Jeffrey ; Zhang, Qinghong ; Goodman, Richard ; Frisch, Steven M. / C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 8. pp. 4568-4573.
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