PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation.
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.
N'Diaye
Elsa-Noah
EN
Department of Microbial Pathogenesis, Genentech, 1 DNA Way, South San Francisco, California 94080, USA.
Kajihara
Kimberly K
KK
Hsieh
Ivy
I
Morisaki
Hiroshi
H
Debnath
Jayanta
J
Brown
Eric J
EJ
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D003470:Culture Media / Q000494:pharmacology; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D016253:Microscopy, Immunoelectron; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D014452:Ubiquitins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*
C502778:ATG5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003470:Culture Media; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C107792:UBQLN1 protein, human; C538987:UBQLN1 protein, mouse; C405662:UBQLN2 protein, human; C538988:UBQLN2 protein, mouse; D014452:Ubiquitins; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes