C-terminal binding proteins: emerging roles in cell survival and tumorigenesis

Within a cell, the levels and activity of multiple pro- and anti-apoptotic molecules act in concert to regulate commitment to apoptosis. Whilst the balance between survival and death can be tipped by the effects of single molecules, cellular apoptosis control pathways very often incorporate key transcription factors that co-ordinately regulate the expression of multiple apoptosis control genes. C-terminal binding proteins (CtBPs), which were originally identified through their binding to the Adenovirus E1A oncoprotein, have been described as such transcriptional regulators of the apoptosis program. Specifically, CtBPs function as transcriptional co-repressors, and have been demonstrated to promote cell survival by suppressing the expression of several pro-apoptotic genes. In this review we summarize the evidence supporting a key role for CtBP proteins in cell survival. We also describe the known mechanisms of transcriptional control by CtBPs, and review the multiplicity of intracellular signaling and transcriptional control pathways with which they are known to be involved. Finally we consider these findings in the context of additional known roles of CtBP molecules, and the potential implications that this combined knowledge may have for our comprehension of diseases of cell survival, notably cancer.