A rare DNA contact mutation in cancer confers p53 gain-of-function and tumor cell survival via TNFAIP8 induction

The p53 tumor suppressor gene encodes a sequence-specific transcription factor. Mutations in the coding sequence of p53 occur frequently in human cancer and often result in single amino acid substitutions (missense mutations) in the DNA binding domain (DBD), blocking normal tumor suppressive functions. In addition to the loss of canonical functions, some missense mutations in p53 confer gain-of-function (GOF) activities to tumor cells. While many missense mutations in p53 cluster at six “hotspot” amino acids, the majority of mutations in human cancer occur elsewhere in the DBD and at a much lower frequency.

Source: Molecular Oncology - June 6, 2016 Category: Cancer & Oncology Authors: Jessica A. Monteith, Hestia Mellert, Morgan A. Sammons, Laudita A. Kuswanto, Stephen M. Sykes, Lois Resnick-Silverman, James J. Manfredi, Shelley L. Berger, Steven B. McMahon Source Type: research