Cyclin D3-dependent control of the dNTP pool and HIV-1 replication in human macrophages

Alba Ruiz, Eduardo Pauls, Roger Badia, Javier Torres-Torronteras, Eva Riveira-Muñoz, Bonaventura Clotet, Ester Ballana, José A. Esté, Ramon Marti Castello

Research output: Contribution to journalArticleResearchpeer-review

29 Citations (Scopus)

Abstract

© 2015 Taylor & Francis Group, LLC. 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.
Original languageEnglish
Pages (from-to)1657-1665
JournalCell Cycle
Volume14
Issue number11
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • Cyclin
  • Cyclin-dependent kinase
  • HIV-1
  • SAMHD1
  • Virus restriction

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