TRIM Proteins Regulate Autophagy and Can Target Autophagic Substrates by Direct Recognition

Michael A. Mandell, Ashish Jain, John Arko-Mensah, Santosh Chauhan, Tomonori Kimura, Christina Dinkins, Guido Silvestri, Jan Münch, Frank Kirchhoff, Anne Simonsen, Yongjie Wei, Beth Levine, Terje Johansen, Vojo Deretic

Research output: Contribution to journalArticle

162 Scopus citations

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 asplatforms 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.

Original languageEnglish (US)
Pages (from-to)394-409
Number of pages16
JournalDevelopmental Cell
Volume30
Issue number4
DOIs
StatePublished - Aug 25 2014

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Mandell, M. A., Jain, A., Arko-Mensah, J., Chauhan, S., Kimura, T., Dinkins, C., Silvestri, G., Münch, J., Kirchhoff, F., Simonsen, A., Wei, Y., Levine, B., Johansen, T., & Deretic, V. (2014). TRIM Proteins Regulate Autophagy and Can Target Autophagic Substrates by Direct Recognition. Developmental Cell, 30(4), 394-409. https://doi.org/10.1016/j.devcel.2014.06.013