Disease-related p63 DBD mutations impair DNA binding by distinct mechanisms and varying degree.

ABSTRACT: The transcription factor p63 shares a high sequence identity with the tumour suppressor p53 which manifests itself in high structural similarity and preference for DNA sequences. Mutations in the DNA binding domain (DBD) of p53 have been studied in great detail, enabling a general mechanism-based classification. In this study we provide a detailed investigation of all currently known mutations in the p63 DBD, which are associated with developmental syndromes, by measuring their impact on transcriptional activity, DNA binding affinity, zinc binding capacity and thermodynamic stability. Some of the mutations we have further characterized with respect to their ability to convert human dermal fibroblasts into induced keratinocytes. Here we propose a classification of the p63 DBD mutations base

SUBMITTER: Osterburg C 

PROVIDER: S-EPMC10113246 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature