Noxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis

TLDR

p53 induces apoptosis in stressed cells, and Noxa is a BH3‑only Bcl‑2 family protein lacking other BH domains. We identify Noxa as a previously unknown pro‑apoptotic gene whose p53‑dependent induction in irradiated primary mouse cells leads to mitochondrial localization, interaction with anti‑apoptotic Bcl‑2 family members, caspase‑9 activation, and whose blockade suppresses apoptosis, demonstrating its role as a mediator of p53‑dependent apoptosis.

Abstract

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.