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

doi:10.1016/j.devcel.2014.06.013

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 journal › Article › peer-review

253 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 language	English (US)
Pages (from-to)	394-409
Number of pages	16
Journal	Developmental cell
Volume	30
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2014.06.013
State	Published - Aug 25 2014

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2014.06.013

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@article{01e58320510848f19f5d9843d0eaf14e,

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 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.",

author = "Mandell, {Michael A.} and Ashish Jain and John Arko-Mensah and Santosh Chauhan and Tomonori Kimura and Christina Dinkins and Guido Silvestri and Jan M{\"u}nch and Frank Kirchhoff and Anne Simonsen and Yongjie Wei and Beth Levine and Terje Johansen and Vojo Deretic",

note = "Funding Information: We thank George Kyei, Manohar Pilli, Nicolas Dupont, Eliseo Castillo, Steven Bradfute, Michal Mudd, and J.L. Guan. This work was supported by grants AI042999 and AI111935 from the NIH and a grant from the Bill and Melinda Gates Foundation, and in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the NIH through grant UL1 TR000041. M.A.M. and C.D. were supported by NIH training grant T32AI007538. T.K. was supported by Manpei Suzuki Diabetes Foundation. F.K. acknowledges the German Research Foundation and the Zeiss Foundation. G.S. was supported by NIH grant P51OD011132 to the Yerkes National Primate Research Center of Emory University. B.L. was supported by NIH grant CA109618 and Cancer Prevention and Research Institute of Texas grant RP120718-P1. T.J. was supported by grant 196898 from the Norwegian Research Council and grant 71043-PR-2006-0320 from the Norwegian Cancer Society. ",

year = "2014",

month = aug,

day = "25",

doi = "10.1016/j.devcel.2014.06.013",

language = "English (US)",

volume = "30",

pages = "394--409",

journal = "Developmental cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - TRIM Proteins Regulate Autophagy and Can Target Autophagic Substrates by Direct Recognition

AU - Mandell, Michael A.

AU - Jain, Ashish

AU - Arko-Mensah, John

AU - Chauhan, Santosh

AU - Kimura, Tomonori

AU - Dinkins, Christina

AU - Silvestri, Guido

AU - Münch, Jan

AU - Kirchhoff, Frank

AU - Simonsen, Anne

AU - Wei, Yongjie

AU - Levine, Beth

AU - Johansen, Terje

AU - Deretic, Vojo

N1 - Funding Information: We thank George Kyei, Manohar Pilli, Nicolas Dupont, Eliseo Castillo, Steven Bradfute, Michal Mudd, and J.L. Guan. This work was supported by grants AI042999 and AI111935 from the NIH and a grant from the Bill and Melinda Gates Foundation, and in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences of the NIH through grant UL1 TR000041. M.A.M. and C.D. were supported by NIH training grant T32AI007538. T.K. was supported by Manpei Suzuki Diabetes Foundation. F.K. acknowledges the German Research Foundation and the Zeiss Foundation. G.S. was supported by NIH grant P51OD011132 to the Yerkes National Primate Research Center of Emory University. B.L. was supported by NIH grant CA109618 and Cancer Prevention and Research Institute of Texas grant RP120718-P1. T.J. was supported by grant 196898 from the Norwegian Research Council and grant 71043-PR-2006-0320 from the Norwegian Cancer Society.

PY - 2014/8/25

Y1 - 2014/8/25

N2 - 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.

AB - 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.

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EP - 409

JO - Developmental cell

JF - Developmental cell

IS - 4

ER -

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

Abstract

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