The expression of PUMA is regulated by the tumor suppressor p53. PUMA is involved in p53-dependent and -independent apoptosis induced by a variety of signals, and is regulated by transcription factors, not by post-translational modifications. After activation, PUMA interacts with antiapoptotic Bcl-2 family members, thus freeing Bax and/or Bak which are then able to signal apoptosis to the mitochondria. Following mitochondrial dysfunction, the caspase cascade is activated ultimately leading to cell death. Several studies have shown that PUMA function is affected or absent in cancer cells. Additionally, many human tumors contain p53 mutations, which results in no induction of PUMA, even after DNA damage induced through irradiation or chemotherapy drugs.Other cancers, which exhibit overexpression of antiapotptic Bcl-2 family proteins, counteract and overpower PUMA-induced apoptosis.
