Regulation of SQSTM1/p62 via UBA domain ubiquitination and its role in disease |
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Authors: | YouJin Lee Conrad C Weihl |
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Institution: | Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA |
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Abstract: | Macroautophagy/autophagy can be a selective degradative process via the utilization of various autophagic receptor proteins. Autophagic receptors selectively recognize ubiquitinated cargoes and deliver them to phagophores, the precursors to autophagosomes, for their degradation. For example, SQSTM1/p62 directly binds to ubiquitinated protein aggregates via its UBA domain and sequesters them into inclusion bodies via its PB1 domain. SQSTM1also interacts with phagophores via its LC3-interacting (LIR) motif. However, a regulatory mechanism for autophagic receptors is not yet understood. |
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Keywords: | autophagy Keap1-Cullin3-Nrf2 pathway neurodegenerative diseases p62/SQSTM1 protein aggregates ubiquitination |
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