USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1

Shouheng Jin, Shuo Tian, Yamei Chen, Chuanxia Zhang, Weihong Xie, Xiaojun Xia, Jun Cui, Rong Fu Wang

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Autophagy, mediated by a number of autophagy-related (ATG) proteins, plays an important role in the bulk degradation of cellular constituents. Beclin-1 (also known as Atg6 in yeast) is a core protein essential for autophagic initiation and other biological processes. The activity of Beclin-1 is tightly regulated by multiple post-translational modifications, including ubiquitination, yet the molecular mechanism underpinning its reversible deubiquitination remains poorly defined. Here, we identified ubiquitin-specific protease 19 (USP19) as a positive regulator of autophagy, but a negative regulator of type I interferon (IFN) signaling. USP19 stabilizes Beclin-1 by removing the K11-linked ubiquitin chains of Beclin-1 at lysine 437. Moreover, we found that USP19 negatively regulates type I IFN signaling pathway, by blocking RIG-I-MAVS interaction in a Beclin-1-dependent manner. Depletion of either USP19 or Beclin-1 inhibits autophagic flux and promotes type I IFN signaling as well as cellular antiviral immunity. Our findings reveal novel dual functions of the USP19-Beclin-1 axis by balancing autophagy and the production of type I IFNs.

Original languageEnglish (US)
Pages (from-to)866-880
Number of pages15
JournalEMBO Journal
Volume35
Issue number8
DOIs
StatePublished - Apr 15 2016

Keywords

  • Beclin-1
  • autophagy
  • cross talk
  • type I interferon
  • ubiquitination

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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