The tumor suppressor protein p53 causes death of cells exposed to stresses that cause DNA damage. The p53 protein causes increased expression of the protein Bax, which in turn causes cell death. However, evidence indicates that expression of other genes must also contribute to p53-induced cell death. Oda et al. screened for genes expressed in response to x-ray irradiation in normal cells but not in mouse cells that lack p53. They identified a gene called Noxa that appears to be directly regulated by p53. Overexpresion of Noxa caused apoptosis, and Noxa interacted with anti-apoptotic Bcl-2 family proteins at the mitochondria. Antisense RNA to Noxa prevented expression of Noxa in response to p53 and inhibited p53-induced apoptosis. Thus, Noxa appears to represent a new target regulated through p53 that contributes to stress-induced cell death.
Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Tanaguchi, T., and Tanaka, N. (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288: 1053-1058. [Abstract] [Full Text]