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.

Interferon regulatory factors (IRFs) constitute a family of transcription factors that commonly possess a novel helix-turn-helix DNA-binding motif. Following the initial identification of two structurally related members, IRF-1 and IRF-2, seven additional members have now been reported. In addition, virally encoded IRFs, which may interfere with cellular IRFs, have also been identified. Thus far, intensive functional analyses have been done on IRF-1, revealing a remarkable functional diversity of this transcription factor in the regulation of cellular response in host defense. Indeed, IRF-1 selectively modulates different sets of genes, depending on the cell type and/or the nature of cellular stimuli, in order to evoke appropriate responses in each. More recently, much attention has also been focused on other IRF family members. Their functional roles, through interactions with their own or other members of the family of transcription factors, are becoming clearer in the regulation of host defense, such as innate and adaptive immune responses and oncogenesis.