Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1
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 i...
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doaj-2a73f623ac5248129fb0fa679570091d2020-11-25T00:19:02ZengElsevierCell Reports2211-12472013-04-01341036104310.1016/j.celrep.2013.03.017Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1Alexandra Cribier0Benjamin Descours1Ana Luiza Chaves Valadão2Nadine Laguette3Monsef Benkirane4Institut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier 34000, FranceInstitut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier 34000, FranceInstitut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier 34000, FranceInstitut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier 34000, FranceInstitut de Génétique Humaine, CNRS UPR1142, Laboratoires de Virologie Moléculaire, Montpellier 34000, France 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. http://www.sciencedirect.com/science/article/pii/S2211124713001241 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alexandra Cribier Benjamin Descours Ana Luiza Chaves Valadão Nadine Laguette Monsef Benkirane |
spellingShingle |
Alexandra Cribier Benjamin Descours Ana Luiza Chaves Valadão Nadine Laguette Monsef Benkirane Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 Cell Reports |
author_facet |
Alexandra Cribier Benjamin Descours Ana Luiza Chaves Valadão Nadine Laguette Monsef Benkirane |
author_sort |
Alexandra Cribier |
title |
Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 |
title_short |
Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 |
title_full |
Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 |
title_fullStr |
Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 |
title_full_unstemmed |
Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1 |
title_sort |
phosphorylation of samhd1 by cyclin a2/cdk1 regulates its restriction activity toward hiv-1 |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-04-01 |
description |
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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url |
http://www.sciencedirect.com/science/article/pii/S2211124713001241 |
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