CtBPs Promote Cell Survival through the Maintenance of Mitotic Fidelity

Abstract

CtBPs (CtBP1 and CtBP2) act in the nucleus as transcriptional corepressors and in the cytoplasm as regulators of Golgi apparatus fission. Studies in which the expression or function of CtBPs has been inhibited have independently identified roles for CtBPs in both suppressing apoptosis and promoting cell cycle progression. Here, we have analyzed the consequences of ablating CtBP expression in breast cancer-derived cell lines. We found that loss of CtBP expression suppresses cell proliferation through a combination of apoptosis, reduction in cell cycle progression, and aberrations in transit through mitosis. The third phenotype includes errors in mitotic chromosome segregation that are associated with decreased association of the chromosome passenger protein aurora B with mitotic chromatin and that are likely to be a primary cause of the proapoptotic and antiproliferative effects of CtBP loss. We also show that loss of CtBP expression results in the activation of the transcription factor p53 and that loss of p53 function renders cells more susceptible to CtBP small interfering RNA-induced apoptosis.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://mcb.asm.org/ .

ACKNOWLEDGMENTS

This work is supported by grants (no. 2003:713 and 2007MayPR15) from the U.K. Breast Cancer Campaign.

We are grateful to Peter Lackie, University of Southampton, for assistance with the live-cell imaging of breast cancer cells.