TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition

Dev Cell. 2014 Aug 25;30(4):394-409. doi: 10.1016/j.devcel.2014.06.013. Epub 2014 Aug 7.

Abstract

Autophagy, a homeostatic process whereby eukaryotic cells target cytoplasmic cargo for degradation, plays a broad role in health and disease states. Here we screened the TRIM family for roles in autophagy and found that half of TRIMs modulated autophagy. In mechanistic studies, we show that TRIMs associate with autophagy factors and act as platforms assembling ULK1 and Beclin 1 in their activated states. Furthermore, TRIM5α acts as a selective autophagy receptor. Based on direct sequence-specific recognition, TRIM5α delivered its cognate cytosolic target, a viral capsid protein, for autophagic degradation. Thus, our study establishes that TRIMs can function both as regulators of autophagy and as autophagic cargo receptors, and reveals a basis for selective autophagy in mammalian cells.

Publication types

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

MeSH terms

  • Antiviral Restriction Factors
  • Apoptosis Regulatory Proteins / metabolism
  • Autophagy*
  • Autophagy-Related Protein-1 Homolog
  • Beclin-1
  • Binding Sites
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases

Substances

  • Antiviral Restriction Factors
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Tripartite Motif Proteins
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases
  • Autophagy-Related Protein-1 Homolog
  • Protein Serine-Threonine Kinases
  • ULK1 protein, human