Cyclin D3-dependent control of the dNTP pool and HIV-1 replication in human macrophages
العنوان: | Cyclin D3-dependent control of the dNTP pool and HIV-1 replication in human macrophages |
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المؤلفون: | Ramon Martí, Bonaventura Clotet, Alba Ruiz, Ester Ballana, Javier Torres-Torronteras, Eva Riveira-Muñoz, Eduardo Pauls, José A. Esté, Roger Badia |
المصدر: | Cell Cycle. 14:1657-1665 |
بيانات النشر: | Informa UK Limited, 2015. |
سنة النشر: | 2015 |
مصطلحات موضوعية: | Cyclin D, Deoxyribonucleotides, Cyclin A, Virus Replication, Models, Biological, SAM Domain and HD Domain-Containing Protein 1, Cyclin-dependent kinase, Report, Humans, Cyclin D3, Phosphorylation, Molecular Biology, Monomeric GTP-Binding Proteins, biology, Macrophages, Cyclin-Dependent Kinase 6, Cell Biology, Cell cycle, Cell biology, enzymes and coenzymes (carbohydrates), Biochemistry, Gene Knockdown Techniques, HIV-1, biology.protein, RNA Interference, Cyclin-dependent kinase 6, Cyclin A2, Developmental Biology, SAMHD1 |
الوصف: | Cyclins control the activation of cyclin-dependent kinases (CDK), which in turn, control the cell cycle and cell division. Intracellular availability of deoxynucleotides (dNTP) plays a fundamental role in cell cycle progression. SAM domain and HD domain-containing protein 1 (SAMHD1) degrades nucleotide triphosphates and controls the size of the dNTP pool. SAMHD1 activity appears to be controlled by CDK. Here, we show that knockdown of cyclin D3 a partner of CDK6 and E2 a partner of CDK2 had a major impact in SAMHD1 phosphorylation and inactivation and led to decreased dNTP levels and inhibition of HIV-1 at the reverse transcription step in primary human macrophages. The effect of cyclin D3 RNA interference was lost after degradation of SAMHD1 by HIV-2 Vpx, demonstrating the specificity of the mechanism. Cyclin D3 inhibition correlated with decreased activation of CDK2. Our results confirm the fundamental role of the CDK6-cyclin D3 pair in controlling CDK2-dependent SAMHD1 phosphorylation and dNTP pool in primary macrophages. |
تدمد: | 1551-4005 1538-4101 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2fe91e91ab40b981c1cb5cd508bef929Test https://doi.org/10.1080/15384101.2015.1030558Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....2fe91e91ab40b981c1cb5cd508bef929 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15514005 15384101 |
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