A Regulatory Circuit Comprising the CBP and SIRT7 Regulates FAM134B-mediated ER-phagy

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2023 Apr 12

PMID 37043189

Authors

Xinyi Wang

Xiao Jiang

Boran Li

Jiahua Zheng

Jiansheng Guo

Lei Gao

Mengjie Du

Xialian Weng

Lin Li

She Chen

Jingzi Zhang

Lei Fang

Ting Liu

Liang Wang

Wei Liu

Dante Neculai

Qiming Sun

Affiliations

Soon will be listed here.

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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