Abstract
Ubiquilins (UBQLNs) are adaptor proteins thought to deliver ubiquitinated substrates to proteasomes. Here, we show a role for UBQLN in autophagy: enforced expression of UBQLN protects cells from starvation-induced death, whereas depletion of UBQLN renders cells more susceptible. The UBQLN protective effect requires the autophagy-related genes ATG5 and ATG7, two essential components of autophagy. The ubiquitin-associated domain of UBQLN mediates both its association with autophagosomes and its protective effect against starvation. Depletion of UBQLN delays the delivery of autophagosomes to lysosomes. This study identifies a new role for UBQLN in regulating the maturation of autophagy, expanding the involvement of ubiquitin-related proteins in this process.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport / antagonists & inhibitors
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Adaptor Proteins, Vesicular Transport / genetics
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Adaptor Proteins, Vesicular Transport / physiology
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Animals
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Autophagy / drug effects
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Autophagy / physiology*
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Autophagy-Related Protein 5
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Autophagy-Related Protein 7
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Autophagy-Related Proteins
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / physiology*
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Culture Media / pharmacology
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HeLa Cells / cytology
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HeLa Cells / drug effects
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Humans
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Mice
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Microscopy, Immunoelectron
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Microtubule-Associated Proteins / antagonists & inhibitors
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Microtubule-Associated Proteins / physiology
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Phagosomes / metabolism
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Protein Interaction Mapping
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Protein Structure, Tertiary
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RNA Interference
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RNA, Small Interfering / physiology
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Recombinant Fusion Proteins / antagonists & inhibitors
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Recombinant Fusion Proteins / physiology
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Ubiquitin-Activating Enzymes / antagonists & inhibitors
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Ubiquitin-Activating Enzymes / genetics
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Ubiquitin-Activating Enzymes / physiology
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Ubiquitins / antagonists & inhibitors
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Ubiquitins / genetics
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Ubiquitins / physiology*
Substances
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ATG5 protein, human
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Autophagy-Related Protein 5
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Autophagy-Related Proteins
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Carrier Proteins
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Cell Cycle Proteins
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Culture Media
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MAP1LC3A protein, human
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Microtubule-Associated Proteins
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RNA, Small Interfering
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Recombinant Fusion Proteins
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UBQLN1 protein, human
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UBQLN1 protein, mouse
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UBQLN2 protein, human
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UBQLN2 protein, mouse
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Ubiquitins
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ATG7 protein, human
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Autophagy-Related Protein 7
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Ubiquitin-Activating Enzymes