Requirement for P62 Acetylation in the Aggregation of Ubiquitylated Proteins Under Nutrient Stress

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Dec 21

PMID 31857589

Citations 58

Authors

Zhiyuan You

Wen-Xue Jiang

Ling-Yun Qin

Zhou Gong

Wei Wan

Jin Li

Yusha Wang

Hongtao Zhang

Chao Peng

Tianhua Zhou

Chun Tang

Wei Liu

Affiliations

Soon will be listed here.

Abstract

Autophagy receptor p62/SQSTM1 promotes the assembly and removal of ubiquitylated proteins by forming p62 bodies and mediating their encapsulation in autophagosomes. Here we show that under nutrient-deficient conditions, cellular p62 specifically undergoes acetylation, which is required for the formation and subsequent autophagic clearance of p62 bodies. We identify K420 and K435 in the UBA domain as the main acetylation sites, and TIP60 and HDAC6 as the acetyltransferase and deacetylase. Mechanically, acetylation at both K420 and K435 sites enhances p62 binding to ubiquitin by disrupting UBA dimerization, while K435 acetylation also directly increases the UBA-ubiquitin affinity. Furthermore, we show that acetylation of p62 facilitates polyubiquitin chain-induced p62 phase separation. Our results suggest an essential role of p62 acetylation in the selective degradation of ubiquitylated proteins in cells under nutrient stress, by specifically regulating the assembly of p62 bodies.

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