PP1 regulatory subunit NIPP1 regulates transcription of E2F1 target genes following DNA damage.

ABSTRACT: DNA damage induces transcriptional repression of E2F1 target genes and a reduction in histone H3-Thr¹¹ phosphorylation (H3-pThr¹¹ ) at E2F1 target gene promoters. Dephosphorylation of H3-pThr11 is partly mediated by Chk1 kinase and protein phosphatase 1γ (PP1γ) phosphatase. Here, we isolated NIPP1 as a regulator of PP1γ-mediated H3-pThr¹¹ by surveying nearly 200 PP1 interactor proteins. We found that NIPP1 inhibits PP1γ-mediated dephosphorylation of H3-pThr¹¹ both in vivo and in vitro. By generating NIPP1-depleted cells, we showed that NIPP1 is required for cell proliferation and the expression of E2F1 target genes. Upon DNA damage, activated protein kinase A (PKA) phosphorylated the NIPP1-Ser¹⁹⁹ residue, adjacent to the PP1 binding mo

SUBMITTER: Hanaki S 

PROVIDER: S-EPMC8253265 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature