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http://purl.uniprot.org/citations/30704899http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30704899http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30704899http://www.w3.org/2000/01/rdf-schema#comment"mTORC1 and GSK3 play critical roles in early stages of (macro)autophagy, but how they regulate late steps of autophagy remains poorly understood. Here we show that mTORC1 and GSK3-TIP60 signaling converge to modulate autophagosome maturation through Pacer, an autophagy regulator that was identified in our recent study. Hepatocyte-specific Pacer knockout in mice results in impaired autophagy flux, glycogen and lipid accumulation, and liver fibrosis. Under nutrient-rich conditions, mTORC1 phosphorylates Pacer at serine157 to disrupt the association of Pacer with Stx17 and the HOPS complex and thus abolishes Pacer-mediated autophagosome maturation. Importantly, dephosphorylation of Pacer under nutrient-deprived conditions promotes TIP60-mediated Pacer acetylation, which facilitates HOPS complex recruitment and is required for autophagosome maturation and lipid droplet clearance. This work not only identifies Pacer as a regulator in hepatic autophagy and liver homeostasis in vivo but also reveals a signal integration mechanism involved in late stages of autophagy and lipid metabolism."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.org/dc/terms/identifier"doi:10.1016/j.molcel.2018.12.017"xsd:string
http://purl.uniprot.org/citations/30704899http://purl.org/dc/terms/identifier"doi:10.1016/j.molcel.2018.12.017"xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Chen S."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Chen S."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Cheng X."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Cheng X."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Gong W."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Gong W."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Jiang X."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Jiang X."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Li L."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Li L."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Liu T."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Liu T."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Ma X."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Ma X."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Liu W."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Liu W."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Sun Q."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Sun Q."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Tian R."xsd:string
http://purl.uniprot.org/citations/30704899http://purl.uniprot.org/core/author"Tian R."xsd:string