The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch

Christopher H. Mauney, Leann C. Rogers, Reuben S. Harris, Larry W. Daniel, Nelmi O. Devarie-Baez, Hanzhi Wu, Cristina M. Furdui, Leslie B. Poole, Fred W. Perrino, Thomas Hollis

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Aims: Proliferative signaling involves reversible posttranslational oxidation of proteins. However, relatively few molecular targets of these modifications have been identified. We investigate the role of protein oxidation in regulation of SAMHD1 catalysis. Results: Here we report that SAMHD1 is a major target for redox regulation of nucleotide metabolism and cell cycle control. SAMHD1 is a triphosphate hydrolase, whose function involves regulation of deoxynucleotide triphosphate pools. We demonstrate that the redox state of SAMHD1 regulates its catalytic activity. We have identified three cysteine residues that constitute an intrachain disulfide bond "redox switch" that reversibly inhibits protein tetramerization and catalysis. We show that proliferative signals lead to SAMHD1 oxidation in cells and oxidized SAMHD1 is localized outside of the nucleus. Innovation and Conclusions: SAMHD1 catalytic activity is reversibly regulated by protein oxidation. These data identify a previously unknown mechanism for regulation of nucleotide metabolism by SAMHD1. Antioxid. Redox Signal. 27, 1317-1331.

Original languageEnglish (US)
Pages (from-to)1317-1331
Number of pages15
JournalAntioxidants and Redox Signaling
Issue number16
StatePublished - Dec 1 2017
Externally publishedYes


  • Aicardi-Goutieres syndrome
  • HIV restriction
  • SAMHD1
  • enzyme catalysis
  • protein oxidation
  • redox switch

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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