ArticleThe EMBO journal2015
TRIM5α requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 100 citations in OpenAlex.
- Ubiquitin E3 ligase activity in TRIpartite Motif (TRIM) family proteins.Biochemical Society transactions · 2026Review
- Article
- A real-time FRET ubiquitin transfer assay for quantitative characterization of ternary complexes in targeted protein degradation.Cell reports methods · 2026Article
- Article
- Study of retroviral restrictions in a Tadarida bat cell line enlightens specific early blocks and TRIM5 locus multiplication.Journal of virology · 2026Article
- TARDBP as a regulator of HIV-1 assembly and infection: a review of targeting the viral capsid precursor Pr55Gag and limiting viral core entry.Cell communication and signaling : CCS · 2026Review
- Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1.International journal of molecular sciences · 2025Review
- HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.The Journal of general virology · 2025Review
- The role of ubiquitin-conjugating enzyme in the process of spermatogenesis.Reproductive biology and endocrinology : RB&E · 2024Review
- Review
- HIV-1 with gag processing defects activates cGAS sensing.Retrovirology · 2024Article
- Capsid-dependent lentiviral restrictions.Journal of virology · 2024Review
- Uncovering the mechanisms of MuRF1-induced ubiquitylation and revealing similarities with MuRF2 and MuRF3.Biochemistry and biophysics reports · 2024Article
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- IP6-stabilised HIV capsids evade cGAS/STING-mediated host immune sensing.EMBO reports · 2023Article
- Trim-Away ubiquitinates and degrades lysine-less and N-terminally acetylated substrates.Nature communications · 2023Article
- Structural and functional asymmetry of RING trimerization controls priming and extension events in TRIM5α autoubiquitylation.Nature communications · 2022Article
- Evasion of cGAS and TRIM5 defines pandemic HIV.Nature microbiology · 2022Article
- Article
- The Roles of Ubiquitination in Pathogenesis of Influenza Virus Infection.International journal of molecular sciences · 2022Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
TRIM5α is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that assembles on incoming retroviral capsids and induces their premature dissociation. It inhibits reverse transcription of the viral genome and can also synthesize unanchored polyubiquitin (polyUb) chains to stimulate innate immune responses. Here, we show that TRIM5α employs the E2 Ub-conjugating enzyme Ube2W to anchor the Lys63-linked polyUb chains in a process of TRIM5α auto-ubiquitination. Chain anchoring is initiated, in cells and in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5α. This modification serves as a substrate for the elongation of anchored Lys63-linked polyUb chains, catalyzed by the heterodimeric E2 enzyme Ube2N/Ube2V2. Ube2W targets multiple TRIM5α internal lysines with Ub especially lysines 45 and 50, rather than modifying the N-terminal amino group, which is instead αN-acetylated in cells. E2 depletion or Ub mutation inhibits TRIM5α ubiquitination in cells and restores restricted viral reverse transcription, but not infection. Our data indicate that the stepwise formation of anchored Lys63-linked polyUb is a critical early step in the TRIM5α restriction mechanism and identify the E2 Ub-conjugating cofactors involved.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.