title: Role of p62/SQSTM1 in liver physiology and pathogenesis.
abstract: p62/sequestosome-1/A170/ZIP (hereafter referred to as p62) is a scaffold protein that has multiple functions, such as signal transduction, cell proliferation, cell survival, cell death, inflammation, tumourigenesis and oxidative stress response. While p62 is an autophagy substrate and is degraded by autophagy, p62 serves as an autophagy receptor for selective autophagic clearance of protein aggregates and organelles. Moreover, p62 functions as a signalling hub for various signalling pathways, including NF-κB, Nrf2 and mTOR. In this review, we discuss the pathophysiological role of p62 in the liver, including formation of hepatic inclusion bodies, cholestasis, obesity, insulin resistance, liver cell death and tumourigenesis.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Manley
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Williams
authors.forename: Wen-Xing
authors.initials: WX
authors.lastname: Ding
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495635:NFE2L2 protein, human; D009363:Neoplasm Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: autophagy; liver; p62/SQSTM1