2. Academic Validation
  3. TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition

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.
Michael A Mandell 1,  Ashish Jain 2,  John Arko-Mensah 1,  Santosh Chauhan 1,  Tomonori Kimura 1,  Christina Dinkins 1,  Guido Silvestri 3,  Jan Münch 4,  Frank Kirchhoff 4,  Anne Simonsen 5,  Yongjie Wei 6,  Beth Levine 6,  Terje Johansen 2,  Vojo Deretic 7
Affiliations

Affiliations

  • 1 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
  • 2 Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
  • 3 Yerkes National Primate Research Center, Emory University, 3014 Yerkes, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
  • 4 Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081 Ulm, Germany.
  • 5 Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
  • 6 Center for Autophagy Research and Howard Hughes Medical Institute, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
  • 7 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA. Electronic address: vderetic@salud.unm.edu.
PMID: 25127057 DOI: 10.1016/j.devcel.2014.06.013
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.

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