The tumor suppressor protein p53 functions to promote cell death or apoptosis in response to stress. It acts both by modulating gene expression in the nucleus and by interacting with regulatory proteins in the cytoplasm that control apoptosis. Chipuk et al. (see the Perspective by Vousden) provide evidence for a mechanism by which these actions of p53 may be coordinated. The product of one p53 target gene is a protein known as PUMA (p53 up-regulated modulator of apoptosis). In cells exposed to DNA-damaging agents, interaction of PUMA with the antiapoptotic protein Bcl-xL appears to cause release of p53 that was previously bound to Bcl-xL. The released p53 may then be free to activate the cytoplasmic events that lead to apoptosis.