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한빛사논문
- 조회122
Autophagy, Aug 28 2024, | https://doi.org/10.1080/15548627.2024.2394306
Phosphorylation of the selective autophagy receptor TAX1BP1 by TBK1 and IKBKE/IKKi promotes Atg8-family protein-dependent clearance of MAVS aggregates
Jesse White 1 *, Young Bong Choi 2 *, Jiawen Zhang 1, Mai Tram Vo 2, Chaoxia He 2, Kashif Shaikh 1, Edward W Harhaj 1
1Department of Microbiology and Immunology, Penn State College School of Medicine, Hershey, PA, USA.
2Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
*Corresponding authors: correspondence to Jesse White or Young Bong Choi
Abstract
TAX1BP1 is a selective macroautophagy/autophagy receptor that inhibits NFKB and RIGI-like receptor (RLR) signaling to prevent excessive inflammation and maintain homeostasis. Selective autophagy receptors such as SQSTM1/p62 and OPTN are phosphorylated by the kinase TBK1 to stimulate their selective autophagy function. However, it is unknown if TAX1BP1 is regulated by TBK1 or other kinases under basal conditions or during RNA virus infection. Here, we found that TBK1 and IKBKE/IKKi function redundantly to phosphorylate TAX1BP1 and regulate its autophagic turnover through canonical macroautophagy. TAX1BP1 phosphorylation promotes its localization to lysosomes resulting in its degradation. Additionally, we found that during vesicular stomatitis virus infection, TAX1BP1 is targeted to lysosomes in an Atg8-family protein-independent manner. Furthermore, TAX1BP1 plays a critical role in the clearance of MAVS aggregates, and phosphorylation of TAX1BP1 controls its MAVS aggrephagy function. Together, our data support a model whereby TBK1 and IKBKE license TAX1BP1-selective autophagy function to inhibit MAVS and RLR signaling.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-29)
- 국외 연구진
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