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- DOI: 10.1042/BJ20140203
- PMID: 25423367
- UKPMCID: 25423367
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The eukaryotic elongation factor eEF1A1 interacts with SAMHD1.
Morrissey, Catherine; Schwefel, David; Ennis-Adeniran, Valerie; Taylor, Ian A; Crow, Yanick J; Webb, Michelle
The Biochemical journal. 2015;466(1):69-76.
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Full-text held externally
- DOI: 10.1042/BJ20140203
- PMID: 25423367
- UKPMCID: 25423367
Abstract
Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), a Mendelian inflammatory disease which displays remarkable clinical and biochemical overlap with congenital viral infection. SAMHD1 has also been defined as an HIV-1 restriction-factor that, through a novel triphosphohydrolase activity, inhibits early stage HIV-1 replication in myeloid derived dendritic cells (MDDCs), macrophages and resting CD4+ T-cells. The potent activity of SAMHD1 is likely to be the subject of a variety of regulatory mechanisms. Knowledge of proteins that interact with SAMHD1 may not only enhance our understanding of the pathogenesis of AGS, but may also provide further details on the link between the regulation of cellular dNTPs and HIV-1 restriction. Here, we used a yeast two-hybrid screen and pull-down analysis followed by mass spectrometry to identify the eukaryotic elongation factor 1A1 (eEF1A1) as a potential interaction partner of SAMHD1. This interaction was confirmed by unbiased co-immunoprecipitation, and demonstrated in situ by a proximity ligation assay. We show that this interaction is enhanced in mutant SAMHD1 cell lines, and suggest that eEF1A1 may mediate SAMHD1 turnover by targeting it to the proteosome for degradation through association with Cullin4A and Rbx1.