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 journalArticle

5 Citations (Scopus)

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

Fingerprint

Phosphorylation
Deoxyribonucleases
Cyclin B
Mutation
Glycols
Phosphoprotein Phosphatases
Immune System Diseases
Fibroblasts
Mitosis
Phosphors
Serine
Interferons
Autoimmune Diseases
Cell Cycle
Genes
Cells
RNA
DNA
dolichyl-diphosphooligosaccharide - protein glycotransferase

Keywords

  • autoimmune disease
  • cell cycle
  • DNase
  • TREX1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mitotic Phosphorylation of TREX1 C Terminus Disrupts TREX1 Regulation of the Oligosaccharyltransferase Complex. / Kucej, Martin; Fermaintt, Charles S.; Yang, Kun; Irizarry-Caro, Ricardo A.; Yan, Nan.

In: Cell Reports, Vol. 18, No. 11, 14.03.2017, p. 2600-2607.

Research output: Contribution to journalArticle

Kucej, Martin ; Fermaintt, Charles S. ; Yang, Kun ; Irizarry-Caro, Ricardo A. ; Yan, Nan. / Mitotic Phosphorylation of TREX1 C Terminus Disrupts TREX1 Regulation of the Oligosaccharyltransferase Complex. In: Cell Reports. 2017 ; Vol. 18, No. 11. pp. 2600-2607.
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