title: TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
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.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mandell
authors.affiliation: Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
authors.forename: John
authors.initials: J
authors.lastname: Arko-Mensah
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Chauhan
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Dinkins
authors.affiliation: Yerkes National Primate Research Center, Emory University, 3014 Yerkes, 954 Gatewood Road NE, Atlanta, GA 30329, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Silvestri
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081 Ulm, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081 Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Simonsen
authors.affiliation: Center for Autophagy Research and Howard Hughes Medical Institute, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Center for Autophagy Research and Howard Hughes Medical Institute, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Levine
authors.affiliation: Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Terje
authors.initials: T
authors.lastname: Johansen
authors.affiliation: 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.
authors.forename: Vojo
authors.initials: V
authors.lastname: Deretic
mesh_terms: D000090103:Antiviral Restriction Factors; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog; D000071186:Beclin-1; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C484754:ULK1 protein, human