Apoptosis is related to many diseases and development. The p53 tumor-suppressor protein induces apoptosis through transcriptional activation of several genes including p53R2, p53AIP1, and PUMA. A new p53 target gene, Noxa, was recently identified, which encodes a protein belonging to the subfamily of BH3-only proapoptic proteins. Noxa and PUMA are both transcriptional targets of p53 and BH3-only proteins. X-ray irradiation increased p53-dependent Noxa mRNA and protein levels. Noxa, when ectopically expressed, interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. Noxa, like PUMA, localized to mitochondria and induces apoptosis in response to p53. Noxa and PUMA may represent direct mediators of p53-induced apoptosis. Increased levels of p53 and its target gene Noxa was found in the impaired tumor development.