Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis

A critical function of tumor suppressor p53 is the induction of Apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa. Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 Family of proteins; this member contains the BH3 region but not Other BH domains. When ectopically expressed, Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 Family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of Apoptosis. Noxa may thus represent a mediator of p53-dependent Apoptosis.