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. 2013 Apr 25;3(4):1036-43.
doi: 10.1016/j.celrep.2013.03.017. Epub 2013 Apr 17.

Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction activity toward HIV-1

Alexandra Cribier  1 , Benjamin Descours, Ana Luiza Chaves Valadão, Nadine Laguette, Monsef Benkirane
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Free article

Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction activity toward HIV-1

Alexandra Cribier et al. Cell Rep. .
Free article

Abstract

SAMHD1 restricts HIV-1 replication in myeloid and quiescent CD4(+) T cells. Here, we show that SAMHD1 restriction activity is regulated by phosphorylation. SAMHD1 interacts with cyclin A2/cdk1 only in cycling cells. Cyclin A2/CDK1 phosphorylates SAMHD1 at the Threonine 592 residue both in vitro and in vivo. Phosphorylation of SAMHD1 Thr592 correlates with loss of its ability to restrict HIV-1. Indeed, while PMA treatment of proliferating THP1 cells results in reduced Thr592 phosphorylation, activation of resting peripheral blood mononuclear cells (PBMCs) and purified quiescent CD4(+) T cells results in increased phosphorylation of SAMHD1 Thr592. Interestingly, we found that treatment of cells by type 1 interferon reduced Thr592 phosphorylation, reinforcing the link between the phosphorylation of SAMHD1 and its antiviral activity. Unlike wild-type SAMHD1, a phosphorylation-defective mutant was able to restrict HIV-1 replication in both PMA-treated and untreated cells. Our results uncover the phosphorylation of SAMHD1 at Thr592 by cyclin A2/CDK1 as a key regulatory mechanism of its antiviral activity.

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