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

doi:10.15252/embj.201593596

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 journal › Article › peer-review

130 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 language	English (US)
Pages (from-to)	866-880
Number of pages	15
Journal	EMBO Journal
Volume	35
Issue number	8
DOIs	https://doi.org/10.15252/embj.201593596
State	Published - 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)

Access to Document

10.15252/embj.201593596

Cite this

@article{e98d57f9d7644c5ab3566667c570b4b7,

title = "USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1",

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.",

keywords = "Beclin-1, autophagy, cross talk, type I interferon, ubiquitination",

author = "Shouheng Jin and Shuo Tian and Yamei Chen and Chuanxia Zhang and Weihong Xie and Xiaojun Xia and Jun Cui and Wang, {Rong Fu}",

note = "Funding Information: This work was supported by National Key Basic Research Program of China (2015CB859800 and 2014CB910800), National Natural Science Foundation of China (31370869, 31522018), Guangdong Natural Science Funds for Distinguished Young Scholar (S2013050014772), Guangdong Innovative Research Team Program (NO. 2011Y035 and 201001Y01046872443), and the Fundamental Research Funds for the Central Universities (15lgjc02), and NCI, NIH (CA090327, CA101795, and CA121191 to RFW). Publisher Copyright: {\textcopyright} 2016 The Authors.",

year = "2016",

month = apr,

day = "15",

doi = "10.15252/embj.201593596",

language = "English (US)",

volume = "35",

pages = "866--880",

journal = "EMBO Journal",

issn = "0261-4189",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - USP19 modulates autophagy and antiviral immune responses by deubiquitinating Beclin-1

AU - Jin, Shouheng

AU - Tian, Shuo

AU - Chen, Yamei

AU - Zhang, Chuanxia

AU - Xie, Weihong

AU - Xia, Xiaojun

AU - Cui, Jun

AU - Wang, Rong Fu

N1 - Funding Information: This work was supported by National Key Basic Research Program of China (2015CB859800 and 2014CB910800), National Natural Science Foundation of China (31370869, 31522018), Guangdong Natural Science Funds for Distinguished Young Scholar (S2013050014772), Guangdong Innovative Research Team Program (NO. 2011Y035 and 201001Y01046872443), and the Fundamental Research Funds for the Central Universities (15lgjc02), and NCI, NIH (CA090327, CA101795, and CA121191 to RFW). Publisher Copyright: © 2016 The Authors.

PY - 2016/4/15

Y1 - 2016/4/15

N2 - 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.

AB - 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.

KW - Beclin-1

KW - autophagy

KW - cross talk

KW - type I interferon

KW - ubiquitination

UR - http://www.scopus.com/inward/record.url?scp=84961219291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961219291&partnerID=8YFLogxK

U2 - 10.15252/embj.201593596

DO - 10.15252/embj.201593596

M3 - Article

C2 - 26988033

AN - SCOPUS:84961219291

SN - 0261-4189

VL - 35

SP - 866

EP - 880

JO - EMBO Journal

JF - EMBO Journal

IS - 8

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this