Aicardi-Goutieres Syndrome Gene and HIV-1 Restriction Factor SAMHD1 Is a dGTP-regulated Deoxynucleotide Triphosphohydrolas

Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
Journal of Biological Chemistry (Impact Factor: 4.6). 11/2011; 286(51):43596-600. DOI: 10.1074/jbc.C111.317628
Source: PubMed

ABSTRACT 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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