1. USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1.
- Author
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Jin, Shouheng, Tian, Shuo, Chen, Yamei, Zhang, Chuanxia, Xie, Weihong, Xia, Xiaojun, Cui, Jun, and Wang, Rong‐Fu
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AUTOPHAGY ,PEPTIDASE ,ANTIVIRAL agents ,IMMUNE response ,POST-translational modification ,UBIQUITINATION - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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