Mechanical cues control mutant p53 stability through a mevalonate-RhoA axis.

ABSTRACT: Tumour-associated p53 missense mutants act as driver oncogenes affecting cancer progression, metastatic potential and drug resistance (gain-of-function) ¹ . Mutant p53 protein stabilization is a prerequisite for gain-of-function manifestation; however, it does not represent an intrinsic property of p53 mutants, but rather requires secondary events ² . Moreover, mutant p53 protein levels are often heterogeneous even within the same tumour, raising questions on the mechanisms that control local mutant p53 accumulation in some tumour cells but not in their neighbours ^2,3 . By investigating the cellular pathways that induce protection of mutant p53 from ubiquitin-mediated proteolysis, we found that HDAC6/Hsp90-dependent mutant p53 accumulation is sustained by R

SUBMITTER: Ingallina E 

PROVIDER: S-EPMC6179142 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature