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Review
. 2011 Nov;21(8):224-8.
doi: 10.1016/j.tcm.2012.05.015.

p62 Stages an interplay between the ubiquitin-proteasome system and autophagy in the heart of defense against proteotoxic stress

Huabo Su  1 , Xuejun Wang
Affiliations
Review

p62 Stages an interplay between the ubiquitin-proteasome system and autophagy in the heart of defense against proteotoxic stress

Huabo Su et al. Trends Cardiovasc Med. 2011 Nov.

Abstract

As exemplified by desmin-related cardiomyopathy and myocardial ischemia/reperfusion injury, proteasome functional insufficiency plays an essential pathogenic role in the progression of cardiac diseases with elevated proteotoxic stress. Upregulation of p62/SQSTM1 and increased selective autophagy in cardiomyocytes may protect against proteotoxic stress in the heart. p62 may serve as a proteotoxic stress sensor, promote segregation and degradation of misfolded proteins by autophagy, and mediate the cross talk between the ubiquitin-proteasome system and autophagy.

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Conflict of interest statement

Conflict of Interest: None.

Figures

Figure 1
Figure 1. p62 and protein quality control (PQC) in cardiomyocytes
(A) Upregulation of p62 in response to proteotoxic stress sequesters NRF2 from its interaction with Keap1, leading to the stablization and activation of NRF2, which in turn induces p62 expression. (B) Proteasome functional insufficiency leads to the accumulation of protein aggregates and compensatory activation of selective autophagy in a p62-dependent manner. Casein kinase 2 (CK2)-mediated p62 phosphorylation regulates selective degradation of protein aggregates by autophagy. Autophagy activation protects cardiomyocytes from defective UPS-induced proteotoxic stress. (C) Defective autophagy accumulates p62, which binds ubiquitinated proteins and promotes their agregation, hindering proteasomal proteolysis. Both defective autophagy and impaired UPS function are detrimental to cardiomyocyte function and survival.
See this image and copyright information in PMC

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