Threshold for Death

Science's STKE  11 May 2004:
Vol. 2004, Issue 232, pp. tw169-TW169
DOI: 10.1126/stke.2322004TW169

Control of initiator caspases, the proteases that activate signaling pathways that lead to cell death or apoptosis, literally determines whether a cell dies. The regulation of caspase-2 is implicated in a particularly important death response, the response to anticancer drugs that induce genotoxic stress. Tinel and Tschopp report that caspase-2 becomes activated as part of a protein complex they call the PIDDosome. PIDD is a protein expressed in response to the tumor suppressor p53 and interacts with an adaptor protein called RAIDD, which in turn binds to caspase-2. Small increases in the amount of PIDD expressed in cells causes activation of caspase-2 and sensitizes cells to the genotoxic agent doxorubicin.

A. Tinel, J. Tschopp, The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304, 843-846 (2004). [Abstract] [Full Text]