Unique Transcriptional Profiles Underlie Osteosarcomagenesis Driven by Different p53 Mutants.

ABSTRACT: Missense mutations in the DNA binding domain of p53 are characterized as structural or contact mutations based on their effect on the conformation of the protein. These mutations show gain-of-function (GOF) activities, such as promoting increased metastatic incidence compared with p53 loss, often mediated by the interaction of mutant p53 with a set of transcription factors. These interactions are largely context specific. To understand the mechanisms by which p53 DNA binding domain mutations drive osteosarcoma progression, we created mouse models, in which either the p53 structural mutant p53R172H or the contact mutant p53R245W are expressed specifically in osteoblasts, yielding osteosarcoma tumor development. Survival significantly decreased and metastatic incidence increased in mice expr

SUBMITTER: Chachad D 

PROVIDER: S-EPMC10524763 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature