P63 is a key regulator of iRHOM2 signalling in the keratinocyte stress response.

ABSTRACT: Hyperproliferative keratinocytes induced by trauma, hyperkeratosis and/or inflammation display molecular signatures similar to those of palmoplantar epidermis. Inherited gain-of-function mutations in RHBDF2 (encoding iRHOM2) are associated with a hyperproliferative palmoplantar keratoderma and squamous oesophageal cancer syndrome (termed TOC). In contrast, genetic ablation of rhbdf2 in mice leads to a thinning of the mammalian footpad, and reduces keratinocyte hyperproliferation and migration. Here, we report that iRHOM2 is a novel target gene of p63 and that both p63 and iRHOM2 differentially regulate cellular stress-associated signalling pathways in normal and hyperproliferative keratinocytes. We demonstrate that p63-iRHOM2 regulates cell survival and response to oxidative stress via mod

SUBMITTER: Arcidiacono P 

PROVIDER: S-EPMC5844915 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature