p62/SQSTM1 functions as a signaling hub and an autophagy adaptor

FEBS J. 2015 Dec;282(24):4672-8. doi: 10.1111/febs.13540. Epub 2015 Oct 16.

Abstract

p62/SQSTM1 is a stress-inducible cellular protein that is conserved among metazoans but not in plants and fungi. p62/SQSTM1 has multiple domains that mediate its interactions with various binding partners and it serves as a signaling hub for diverse cellular events such as amino acid sensing and the oxidative stress response. In addition, p62/SQSTM1 functions as a selective autophagy receptor for degradation of ubiqutinated substrates. In the present review, we describe the current knowledge about p62 with regard to mammalian target of rapamycin complex 1 activation, the Keap1-Nrf2 pathway and selective autophagy.

Keywords: Keap1-Nrf2 system; mTORC1; p62/Sqstm1; selective autophagy; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Autophagy*
  • Enzyme Activation
  • Humans
  • Intracellular Signaling Peptides and Proteins / agonists
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kelch-Like ECH-Associated Protein 1
  • Mechanistic Target of Rapamycin Complex 1
  • Models, Biological*
  • Models, Molecular*
  • Multiprotein Complexes / agonists
  • Multiprotein Complexes / metabolism
  • NF-E2-Related Factor 2 / agonists
  • NF-E2-Related Factor 2 / metabolism
  • Protein Interaction Domains and Motifs
  • Sequestosome-1 Protein
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • Multiprotein Complexes
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases