TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
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Mandell MA, Jain A, Arko-Mensah J, Chauhan S, Kimura T, Dinkins C, Silvestri G, Munch J, Kirchhoff F, Simonsen A, Wei Y, Levine B, Johansen T, Deretic V
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. Epub 2014 Aug 7.
- PubMed ID
- 25127057 [ View in PubMed]
- 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, TRIM5alpha acts as a selective autophagy receptor. Based on direct sequence-specific recognition, TRIM5alpha 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.