Research ArticleBiochemistry

Mutant and wild-type p53 form complexes with p73 upon phosphorylation by the kinase JNK

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Science Signaling  03 Apr 2018:
Vol. 11, Issue 524, eaao4170
DOI: 10.1126/scisignal.aao4170

Another look at p53-p73 interactions

The transcription factor p53 critically regulates cell survival or death in response to cellular stress. Mutations in p53 are common in cancer and alter its interactions with other proteins and, consequently, with cell fate–specific genes. Mutant p53 binds to and inhibits its family member p73, thereby promoting cell survival instead of cell death in response to cell stress. It was believed that this interaction with p73 was specific to mutant p53. However, Wolf et al. found that wild-type p53 can bind p73 to promote stress-induced cell death. Phosphorylation of wild-type p53 by the cell stress–responsive kinase JNK caused a conformational change that mirrored the regional structure of the mutant and enabled its binding to p73 but, unlike mutant p53, the wild-type protein could still bind to apoptotic gene targets. These findings refine our understanding of p53 interactions and, specifically, p53-p73 coordination in the cell stress response.