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

132 Citations (Scopus)

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

Fingerprint

Autophagy
Degradation
Capsid Proteins
Substrates
Proteins
Cells
Health
Eukaryotic Cells
Viral Proteins
Tripartite Motif Proteins
Proteolysis

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Mandell, M. A., Jain, A., Arko-Mensah, J., Chauhan, S., Kimura, T., Dinkins, C., ... 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

TRIM Proteins Regulate Autophagy and Can Target Autophagic Substrates by Direct Recognition. / Mandell, Michael A.; Jain, Ashish; Arko-Mensah, John; Chauhan, Santosh; Kimura, Tomonori; Dinkins, Christina; Silvestri, Guido; Münch, Jan; Kirchhoff, Frank; Simonsen, Anne; Wei, Yongjie; Levine, Beth; Johansen, Terje; Deretic, Vojo.

In: Developmental Cell, Vol. 30, No. 4, 25.08.2014, p. 394-409.

Research output: Contribution to journalArticle

Mandell, MA, 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, vol. 30, no. 4, pp. 394-409. https://doi.org/10.1016/j.devcel.2014.06.013
Mandell MA, Jain A, Arko-Mensah J, Chauhan S, Kimura T, Dinkins C et al. TRIM Proteins Regulate Autophagy and Can Target Autophagic Substrates by Direct Recognition. Developmental Cell. 2014 Aug 25;30(4):394-409. https://doi.org/10.1016/j.devcel.2014.06.013
Mandell, Michael A. ; Jain, Ashish ; Arko-Mensah, John ; Chauhan, Santosh ; Kimura, Tomonori ; Dinkins, Christina ; Silvestri, Guido ; Münch, Jan ; Kirchhoff, Frank ; Simonsen, Anne ; Wei, Yongjie ; Levine, Beth ; Johansen, Terje ; Deretic, Vojo. / TRIM Proteins Regulate Autophagy and Can Target Autophagic Substrates by Direct Recognition. In: Developmental Cell. 2014 ; Vol. 30, No. 4. pp. 394-409.
@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",
year = "2014",
month = "8",
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

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.

UR - http://www.scopus.com/inward/record.url?scp=84907599058&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907599058&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2014.06.013

DO - 10.1016/j.devcel.2014.06.013

M3 - Article

VL - 30

SP - 394

EP - 409

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 4

ER -