The SAMHD1 dNTP Triphosphohydrolase Is Controlled by a Redox Switch.

ABSTRACT:

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 SAMHD

SUBMITTER: Mauney CH 

PROVIDER: S-EPMC5655415 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature