Role of p62/SQSTM1 in liver physiology and pathogenesis

Exp Biol Med (Maywood). 2013 May;238(5):525-38. doi: 10.1177/1535370213489446.

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.

Keywords: autophagy; liver; p62/SQSTM1.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Autophagy
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology
  • Humans
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / physiopathology
  • Insulin Resistance
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / physiopathology
  • Liver* / metabolism
  • Liver* / pathology
  • Liver* / physiopathology
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Proteins / metabolism*
  • Oxidative Stress
  • Sequestosome-1 Protein
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Neoplasm Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • MTOR protein, human
  • TOR Serine-Threonine Kinases