USP 19 modulates autophagy and antiviral immune responses by deubiquitinating beclin‐1
S Jin, S Tian, Y Chen, C Zhang, W Xie, X Xia… - The EMBO …, 2016 - embopress.org
S Jin, S Tian, Y Chen, C Zhang, W Xie, X Xia, J Cui, RF Wang
The EMBO journal, 2016•embopress.orgAutophagy, 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 (USP 19) as a …
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 (USP 19) as a …
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.
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