Rescue of embryonic stem cells from cellular transformation by proteomic stabilization of mutant p53 and conversion into WT conformation.

ABSTRACT: p53 is a well-known tumor suppressor that is mutated in over 50% of human cancers. These mutations were shown to exhibit gain of oncogenic function compared with the deletion of the gene. Additionally, p53 has fundamental roles in differentiation and development; nevertheless, mutant p53 mice are viable and develop malignant tumors only on adulthood. We set out to reveal the mechanisms by which embryos are protected from mutant p53-induced transformation using ES cells (ESCs) that express a conformational mutant of p53. We found that, despite harboring mutant p53, the ESCs remain pluripotent and benign and have relatively normal karyotype compared with ESCs knocked out for p53. Additionally, using high-content RNA sequencing, we show that p53 is transcriptionally active in response to DNA

SUBMITTER: Rivlin N 

PROVIDER: S-EPMC4024907 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature