ArticleThe Journal of biological chemistry2019
Insulin-induced gene 1 (INSIG1) inhibits HIV-1 production by degrading Gag via activity of the ubiquitin ligase TRC8.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Engineering Stable Lentiviral Vector Producer Cells Improves LVV Production.Biotechnology and bioengineering · 2026Article
- Insights Into circRNA-Mediated Lipid Metabolism in Cancer Progression.Journal of cellular and molecular medicine · 2026Review
- Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms.Cell reports · 2024Article
- Proprotein convertase furin in SARS-CoV-2 and non-small cell lung cancer.Translational lung cancer research · 2020Article
- Production of Vesicular Stomatitis Virus Glycoprotein-Pseudotyped Lentiviral Vector Is Enhanced by Ezrin Silencing.Frontiers in bioengineering and biotechnology · 2020Article
- Ubiquitin E3 Ligase c-Cbl Is a Host Negative Regulator of Nef Protein of HIV-1.Frontiers in microbiology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
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Abstract
Insulin-induced gene 1 (INSIG1) regulates sterol synthesis by mediating the activation of sterol regulatory element-binding protein (SREBP) and the degradation of the HMG-CoA reductase (HMGCR). INSIG1 is up-regulated during HIV-1 infection, but its role in HIV-1 infection is unknown. In this report, using pseudovirus production, protein overexpression, and gene knockouts, we found that INSIG1 inhibits HIV-1 production by accelerating the degradation of the HIV-1 Gag protein. Unlike the degradation of HMGCR via the E3 ubiquitin ligase autocrine motility factor receptor (AMFR), a process that depends on the proteasome, INSIG1 coordinated with another ligase, translocation in renal carcinoma chromosome 8 (TRC8), and promoted Gag degradation through the lysosome pathway. We conclude that INSIG1 functions as a sentinel responsive to HIV-1 production and inhibits HIV-1 replication by degrading Gag, a process occurring at intracellular membrane sites such as the endoplasmic reticulum and endosomes where both INSIG1 and Gag may be located.
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