Structural insights into the transcription-independent apoptotic pathway of p53

Reactivating the p53 pathway in tumors is an important strategy for anticancer therapy. In response to diverse cellular stresses, the tumor suppressor p53 mediates apoptosis in a transcription-independent and transcription-dependent manner. Although extensive studies have focused on the transcription-dependent apoptotic pathway of p53, the transcription-independent apoptotic pathway of p53 has only recently been discovered. Molecular interactions between p53 and Bcl-2 family proteins in the mitochondria play an essential role in the transcription-independent apoptosis of p53. This review describes the structural basis for the transcription-independent apoptotic pathway of p53 and discusses its potential application to anticancer therapy.