Selective autophagic receptor p62 regulates the abundance of transcriptional coregulator ARIP4 during nutrient starvation

Sci Rep. 2015 Sep 28:5:14498. doi: 10.1038/srep14498.

Abstract

Transcriptional coregulators contribute to several processes involving nuclear receptor transcriptional regulation. The transcriptional coregulator androgen receptor-interacting protein 4 (ARIP4) interacts with nuclear receptors and regulates their transcriptional activity. In this study, we identified p62 as a major interacting protein partner for ARIP4 in the nucleus. Nuclear magnetic resonance analysis demonstrated that ARIP4 interacts directly with the ubiquitin-associated (UBA) domain of p62. ARIP4 and ubiquitin both bind to similar amino acid residues within UBA domains; therefore, these proteins may possess a similar surface structure at their UBA-binding interfaces. We also found that p62 is required for the regulation of ARIP4 protein levels under nutrient starvation conditions. We propose that p62 is a novel binding partner for ARIP4, and that its binding regulates the cellular protein level of ARIP4 under conditions of metabolic stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Carrier Proteins
  • Cell Line
  • DNA Helicases / chemistry
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism*
  • Ectopic Gene Expression
  • Enzyme Activation
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping
  • Protein Transport
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Starvation
  • Transcription, Genetic*
  • Ubiquitin / metabolism

Substances

  • Carrier Proteins
  • P62 protein, human
  • RNA-Binding Proteins
  • Ubiquitin
  • DNA Helicases
  • RAD54L2 protein, human