SMG1 and CDK12 Link ΔNp63α Phosphorylation to RNA Surveillance in Keratinocytes.

ABSTRACT: The tumor suppressor p53-like protein p63 is required for self-renewal of epidermal tissues. Loss of p63 or exposure to ultraviolet (UV) irradiation triggers terminal differentiation in keratinocytes. However, it remains unclear how p63 diverts epidermal cells from proliferation to terminal differentiation, thereby contributing to successful tissue self-renewal. Here, we used bottom-up proteomics to identify the proteome at the chromatin in normal human epidermal keratinocytes following UV irradiation and p63 depletion. We found that loss of p63 increased DNA damage and that UV irradiation recruited the cyclin-dependent kinase CDK12 and the serine/threonine protein kinase SMG1 to chromatin only in the presence of p63. A post-translational modification analysis of ΔNp63α with mass spectrome

SUBMITTER: Bamberger C 

PROVIDER: S-EPMC10653645 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature