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TRIM proteins regulate autophagy: TRIM5 is a selective autophagy receptor mediating HIV-1 restriction
Open accessAbstract
The tripartite motif protein family (TRIM) constitutes a class of immune-regulated proteins with antiviral, immune, cancer, and other properties reminiscent of those ascribed to autophagy. We show that TRIMs have dual roles in autophagy: as regulators and as cargo receptors. As regulators, TRIMs nucleate the core autophagy machinery by acting as platforms that assemble ULK1 and BECN1 into a functional complex in preparation for autophagy. TRIMs also act as novel selective autophagy receptors as exemplified by TRIM5/TRIM5α, a known HIV-1 restriction factor with a hitherto poorly defined mode of action. TRIM5 recognizes and targets HIV-1 for autophagic destruction. TRIM5 interactions with mammalian Atg8 proteins are required for this effector function. This establishes TRIM family members as regulators of autophagy, explains the antiretroviral mechanism of TRIM5, and defines a new basis for selective autophagy.
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Trim5 acts as a selective autophagy receptor and plays a key role in autophagy.
“Previous studies have reported that Trim5 acts as a selective autophagy receptor and plays a key role in autophagy.21”
From Novel roles of Nrf3–Trim5 axis in vascular smooth muscle cell dysfunctions and neointimal hyperplasia (2025) · cites this paper as [21]
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Metadata
- Authors
- Mandell, M. A., Kimura, T., Jain, A., Johansen, T., & Deretic, V.
- Affiliations
- University of New Mexico (US)
- UiT The Arctic University of Norway (NO)
- Corresponding author
- Deretic, Vojo
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2014-12-02
- Volume
- 10
- Issue
- 12
- Pages
- 2387-2388
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4502693
- OpenAlex
- W2072744924
- Cited by
- 80
- References
- 0
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 10 · 2019: 8 · 2018: 7 · 2017: 8 · 2016: 7 · 2015: 5
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Keywords
- TRIM proteins, autophagy regulation, selective autophagy, TRIM5, TRIM5α, HIV-1 restriction, autophagy receptors, ULK1, Beclin-1, ATG8, cargo receptors
- MeSH terms
- Autophagy, Carrier Proteins, Humans
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