Mitotic Phosphorylation of TREX1 C Terminus Disrupts TREX1 Regulation of the Oligosaccharyltransferase Complex

Martin Kucej, Charles S. Fermaintt, Kun Yang, Ricardo A. Irizarry-Caro, Nan Yan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

TREX1 mutations are associated with several autoimmune and inflammatory diseases. The N-terminal DNase domain of TREX1 is important for preventing self-DNA from activating the interferon response. The C terminus of TREX1 is required for ER localization and regulation of oligosacchariyltransferase (OST) activity. Here, we show that during mitosis TREX1 is predominately phosphorylated at the C-terminal Serine-261 by Cyclin B/CDK1. TREX1 is dephosphorylated quickly at mitotic exit, likely by PP1/PP2-type serine/threonine phosphatase. Mitotic phosphorylation does not affect TREX1 DNase activity. Phosphomimetic mutations of mitotic phosphorylation sites in TREX1 disrupted the interaction with the OST subunit RPN1. RNA-seq analysis of Trex1−/− mouse embryonic fibroblasts expressing TREX1 wild-type or phosphor-mutants revealed a glycol-gene signature that is elevated when TREX1 mitotic phosphorylation sites are disrupted. Thus, the cell-cycle-dependent post-translation modification of TREX1 regulates its interaction with OST, which may have important implications for immune disease associated with the DNase-independent function of TREX1.

Original languageEnglish (US)
Pages (from-to)2600-2607
Number of pages8
JournalCell Reports
Volume18
Issue number11
DOIs
StatePublished - Mar 14 2017

Keywords

  • DNase
  • TREX1
  • autoimmune disease
  • cell cycle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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