Editors' ChoiceApoptosis

Understanding Killing

Science's STKE  11 Nov 2003:
Vol. 2003, Issue 208, pp. tw440
DOI: 10.1126/stke.2003.208.tw440

The tumor supressor p53 acts in part by causing cell death or apoptosis of tumor cells. p53 appears to act through transcriptional activation of certain genes, but those that specifically mediate the apoptotic response have not been identified. Villunger et al. suspected two genes, puma and noxa, because they are targets of p53 regulation and encode proteins that are similar in structure to other pro-apoptotic proteins. Their analysis of knockout mice lacking the Puma or Noxa proteins shows that death induced by agents that cause DNA damage (and thus activation of p53) is inhibited in fibroblasts lacking Noxa and in fibroblasts and lymphocytes lacking Puma. Lack of Puma also conferred resistance to other death-inducing stimuli that do not act through p53. The findings help to explain both how the p53 tumor suppressor functions and how certain chemotherapeutic agents help battle cancer cells.

A. Villunger, E. M. Michalak, L. Coultas, F. Müllauer, G. Böck, M. J. Ausserlechner, J. M. Adams, A. Strasser, p53- and drug-induced apoptotic responses mediated by BH3-only proteins Puma and Noxa. Science 302, 1036-1038 (2003). [Abstract] [Full Text]