Cited 26 time in
Cited 26 time in
Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress
- Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress
- Peng H.; Yang J.; Li G.; You Q.; Han W.; Li T.; Gao D.; Xie X.; Lee, Byung Hoon; Du J.; Hou J.; Zhang T.; Rao H.; Huang Y.; Li Q.; Zeng R.; Hui L.; Wang H.; Xia Q.; Zhang X.; He Y.; Komatsu M.; Dikic I.; Finley D.; Hu R.
- DGIST Authors
- Lee, Byung Hoon
- Issue Date
- Cell Research, 27(5), 657-674
- Article Type
- autophagy receptor; ubiquitylation; heat shock; dynamic light scattering; ubiquitin; selective autophagy
- Alterations in cellular ubiquitin (Ub) homeostasis, known as Ub stress, feature and affect cellular responses in multiple conditions, yet the underlying mechanisms are incompletely understood. Here we report that autophagy receptor p62/sequestosome-1 interacts with E2 Ub conjugating enzymes, UBE2D2 and UBE2D3. Endogenous p62 undergoes E2-dependent ubiquitylation during upregulation of Ub homeostasis, a condition termed as Ub + stress, that is intrinsic to Ub overexpression, heat shock or prolonged proteasomal inhibition by bortezomib, a chemotherapeutic drug. Ubiquitylation of p62 disrupts dimerization of the UBA domain of p62, liberating its ability to recognize polyubiquitylated cargoes for selective autophagy. We further demonstrate that this mechanism might be critical for autophagy activation upon Ub + stress conditions. Delineation of the mechanism and regulatory roles of p62 in sensing Ub stress and controlling selective autophagy could help to understand and modulate cellular responses to a variety of endogenous and environmental challenges, potentially opening a new avenue for the development of therapeutic strategies against autophagy-related maladies. © 2017 IBCB, SIBS, CAS All rights reserved.
- Nature Publishing Group
- Related Researcher
Lab of Protein Homeostasis and Drug Discovery
Ubiquitin-proteasome system; Protein homeostasis; Small-molecule chemical screening and drug discovery in human disease
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- Department of New BiologyLab of Protein Homeostasis and Drug Discovery1. Journal Articles
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