Aicardi-Goutieres syndrome gene and HIV-1 restriction factor SAMHD1 is a dGTP-regulated deoxynucleotide triphosphohydrolase.

J Biol Chem 2011 Dec 7;286(51):43596-600. Epub 2011 Nov 7.

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.

The SAMHD1 protein is an HIV-1 restriction factor that is targeted by the HIV-2 accessory protein Vpx in myeloid lineage cells. Mutations in the SAMHD1 gene cause Aicardi-Goutières syndrome, a genetic disease that mimics congenital viral infection. To determine the physiological function of the SAMHD1 protein, the SAMHD1 gene was cloned, recombinant protein was produced, and the catalytic activity of the purified enzyme was identified. We show that SAMHD1 contains a dGTP-regulated deoxynucleotide triphosphohydrolase. We propose that Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication.

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http://dx.doi.org/10.1074/jbc.C111.317628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243528PMC
December 2011
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