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

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

Data de publicació online: 30/04/2015 Revista: Cell Cycle

Abstract:

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.

Autors: Ruiz, Alba; Pauls, Eduardo; Badia, Roger; Torres-Torronteras, Javier; Riveira-Munoz, Eva; Clotet, Bonaventura; Marti, Ramon; Ballana, Ester; Este, Jose A.

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