Repo-Man/protein phosphatase 1 SUMOylation mediates binding to lamin A and serine 22 dephosphorylation

Florentin Huguet, Ezgi Gokan, Helen A. Foster, Hasnat A. Amin, Paola Vagnarelli

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Abstract

Lamin A phosphorylation/de-phosphorylation is an important process during cells division as it allows for nuclear envelope (NE) disassembly at mitotic entry and its re-assembly during mitotic exit. Several kinases have been identified as responsible for these phosphorylations, but no protein phosphatase has been implicated in their reversal. One of the mitotic phosphosites in lamin A responsible for its dynamic behaviour is serine 22 (S22) which is de-phosphorylated during mitotic exit. Recent evidence has also linked the nuclear pool of lamin A S22ph in interphase to gene expression regulation. Previous work suggested that the phosphatase responsible for lamin A S22 de-phosphorylation is chromatin bound and interacts with lamin A via SUMO-SIM motives. We have previously reported that Repo-Man/protein phosphatase 1 (PP1) is a chromatin-associated phosphatase that regulates NE reformation. Here we propose that Repo-Man/PP1 phosphatase mediates lamin A S22 de-phosphorylation. We indeed show that depletion of Repo-Man leads to NE defects, causes hyperphosphorylation of lamin A S22 that can be rescued by a wild-type but not a SUMOylation-deficient mutant. Lamin A and Repo-Man interact in vivo and in vitro, and the interaction is mediated by SUMOylation. Moreover, the localization of Repo-Man/PP1 to the chromatin is essential for lamin A S22 de-phosphorylation.
Original languageEnglish
Article number220017
Pages (from-to)1-12
Number of pages12
JournalOpen Biology
Volume12
Issue number4
Early online date13 Apr 2022
DOIs
Publication statusPublished - 13 Apr 2022

Keywords

  • Research
  • Research articles
  • protein phosphatase 1
  • SUMOylation
  • lamin A
  • phosphorylation
  • mitosis
  • Phosphorylation
  • Mitosis
  • Protein phosphatase 1
  • Lamin A
  • Chromatin
  • Humans
  • Serine/metabolism
  • Cell Cycle Proteins/metabolism
  • Lamin Type A/genetics
  • Nuclear Proteins/metabolism
  • Sumoylation
  • Carrier Proteins/metabolism
  • Protein Phosphatase 1/genetics

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