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Molecular and Cellular Biology, August 2009, p. 4539-4551, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.00439-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CtBPs Promote Cell Survival through the Maintenance of Mitotic Fidelity{triangledown} ,{dagger}

Lee M. Bergman,1,{ddagger} Charles N. Birts,1,{ddagger} Matthew Darley,1 Brian Gabrielli,2 and Jeremy P. Blaydes1*

Somers Cancer Research Building, University of Southampton, MP824 Southampton General Hospital, Southampton SO16 6YD, United Kingdom,1 Diamantina Institute for Cancer Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia2

Received 6 April 2009/ Accepted 1 June 2009

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.

* Corresponding author. Mailing address: Somers Cancer Research Building, University of Southampton, MP824 Southampton General Hospital, Southampton SO16 6YD, United Kingdom. Phone: 44 (0)2380 794582. Fax: 44 (0)2380 795152. E-mail: j.p.blaydes{at}soton.ac.uk

{triangledown} Published ahead of print on 8 June 2009.

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

{ddagger} L.M.B. and C.N.B. contributed equally to this work.

Molecular and Cellular Biology, August 2009, p. 4539-4551, Vol. 29, No. 16
0270-7306/09/$08.00+0     doi:10.1128/MCB.00439-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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