Shouheng Jin1,2, Shuo Tian1, Yamei Chen1, Chuanxia Zhang2, Weihong Xie2, Xiaojun Xia3,4, Jun Cui3,1, Rong‐Fu Wang5
1Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
2Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
3Collaborative Innovation Center of Cancer Medicine Sun Yat-sen University Guangzhou China
4Department of Experimental Medicine State Key Laboratory of Oncology in South China Sun Yat-sen University Guangzhou China
5Houston Methodist Research Institute, Houston, TX, USA
Tóm tắt
AbstractAutophagy, 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.
