2. Academic Validation
  3. A regulatory circuit comprising the CBP and SIRT7 regulates FAM134B-mediated ER-phagy

A regulatory circuit comprising the CBP and SIRT7 regulates FAM134B-mediated ER-phagy

  • J Cell Biol. 2023 May 1;222(5):e202201068. doi: 10.1083/jcb.202201068.
Xinyi Wang # 1,  Xiao Jiang # 1,  Boran Li # 1 2,  Jiahua Zheng 1 2,  Jiansheng Guo 3,  Lei Gao 4,  Mengjie Du 5,  Xialian Weng 6,  Lin Li 7,  She Chen 7,  Jingzi Zhang 8,  Lei Fang 8,  Ting Liu 6,  Liang Wang 5,  Wei Liu 1 2,  Dante Neculai 2 6,  Qiming Sun 1 2
Affiliations

Affiliations

  • 1 Department of Biochemistry, and Department of Cardiology of Second Affiliated Hospital, Zhejiang University School of Medicine , Hangzhou, China.
  • 2 International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine , Yiwu, China.
  • 3 Center of Cryo-Electron Microscopy, School of Medicine, Zhejiang University , Hangzhou, China.
  • 4 Microscopy Core Facility, Westlake University , Hangzhou, China.
  • 5 Department of Neurology of Second Affiliated Hospital, Institute of Neuroscience, Mental Health Center, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine , Hangzhou, China.
  • 6 Department of Cell Biology, Department of General Surgery of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China.
  • 7 National Institute of Biological Sciences, Beijing , Beijing, China.
  • 8 Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University , Nanjing, China.
  • # Contributed equally.
PMID: 37043189 DOI: 10.1083/jcb.202201068
Abstract

Macroautophagy (Autophagy) utilizes a serial of receptors to specifically recognize and degrade Autophagy cargoes, including damaged organelles, to maintain cellular homeostasis. Upstream signals spatiotemporally regulate the biological functions of selective Autophagy receptors through protein post-translational modifications (PTM) such as phosphorylation. However, it is unclear how acetylation directly controls Autophagy receptors in selective Autophagy. Here, we report that an ER-phagy receptor FAM134B is acetylated by CBP acetyltransferase, eliciting intense ER-phagy. Furthermore, FAM134B acetylation promoted CAMKII-mediated phosphorylation to sustain a mode of milder ER-phagy. Conversely, SIRT7 deacetylated FAM134B to temper its activities in ER-phagy to avoid excessive ER degradation. Together, this work provides further mechanistic insights into how ER-phagy receptor perceives environmental signals for fine-tuning of ER homeostasis and demonstrates how nucleus-derived factors are programmed to control ER stress by modulating ER-phagy.

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