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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, TRIM5? acts as a selective autophagy receptor. Based on direct sequence-specific recognition, TRIM5? 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.

SUBMITTER: Mandell MA

PROVIDER: S-EPMC4146662 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.

Mandell Michael A MA Jain Ashish A Arko-Mensah John J Chauhan Santosh S Kimura Tomonori T Dinkins Christina C Silvestri Guido G Münch Jan J Kirchhoff Frank F Simonsen Anne A Wei Yongjie Y Levine Beth B Johansen Terje T Deretic Vojo V

Developmental cell 20140807 4

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-specifi ...[more]

PMID: 25127057

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