The transcriptional corepressor CtBP: a foe of multiple tumor suppressors

Abstract

CtBP1 and CtBP2 are closely related and evolutionarily conserved transcriptional corepressors. There is strong evidence linking CtBPs to tumorigenesis and tumor progression. CtBPs promote epithelial-mesenchymal transition and function as apoptosis antagonists. Also, CtBPs mediate repression of several tumor suppressor genes. Certain tumor suppressors also target CtBPs to restrain their tumor-promoting activity. Down-regulation of CtBPs mediated by some tumor suppressors results in p53-independent apoptosis and reduced tumor cell migration and invasion. The role of CtBPs in modulating the activities of different tumor suppressors is reviewed here. The results discussed here suggest that CtBPs may constitute a novel p53-independent anticancer target.

Figure 1

Role of CtBP in tumorigenesis and tumor progression. The transcriptional corepressor activity of CtBP is depicted to be stimulated under hypoxic tumor environment as a result of elevated NADH levels and CtBP dimerization. CtBP is shown to enhance cell proliferation via transcriptional repression of cell cycle inhibitors p16Ink4a and possibly p15Ink4b. The transcriptional repression activity of CtBP is shown to repress E-cadherin and possibly PTEN to promote EMT, tumor cell migration, and invasion. As a result of repression of the proapoptotic genes (PERP, Bax, and Noxa), CtBP is shown to promote cell survival. These activities of CtBP are depicted to be down-regulated by physical association with tumor suppressors HIPK2 or Ink4a/Arf or APC, which promote CtBP degradation as a result of phosphorylation and ubiquitination.