Caspase-2: the reinvented enzyme

On the basis of evidences that caspase-2 gene targeting in several generated mouse models accelerates tumor formation, this enzyme was recently implicated in tumor suppression. The observed function, however, compels other molecular perturbations harboring tumorigenic properties. Therefore, the question remains as to whether or not caspase-2 can be considered a true tumor suppressor? The traditional view of caspase-2 being vital for the apoptotic response to induced cell stress in some systems is in line with these findings. Yet, caspase-2 has also been associated with other processes which equally might interfere with tumorigenic potential, including the oxidative stress response, aging and genome surveillance. By different mechanisms, this enzyme has been proposed to function as a checkpoint regulator in the cell cycle. Together, these data indicate that caspase-2 is a highly versatile factor, a view that is contrasted by the alternative explanation where the enzyme harbors a mechanism affecting a discrete process, which in turn is functionally connected to other cell systems. In any case, it is clear that the general view of caspase-2 as a protein mainly involved in apoptotic cell death is shattered. Hence, we wish to discuss the perspectives of recent achievements in caspase-2-related research.