The eukaryotic elongation factor eEF1A1 interacts with SAMHD1

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 (SAM domain and HD domain-containing protein 1) 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. In the present study, we used a yeast two-hybrid screen and pull-down analysis followed by MS 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 (PLA). 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.

Er:YAG Laser and Cyclosporin A Effect on Cell Cycle Regulation of Human Gingival Fibroblast Cells

“…33,34,41 It participates in several processes required for proliferation, mitotic apparatus formation, and signal transduction. [34][35][36] In a previous study, it was reported that elongation factor 1-alpha 1 is differentially expressed in PDL cell in presence of enamel matrix protein in culture medium. Increase was demonstrated in RNA synthesis, which causes periodontal regeneration and wound healing.…”

Proteomic analyses of nucleus laminaris identified candidate targets of the fragile X mental retardation protein

“…Furthermore, we visualized dendritic localization of eEF2 but not of eEF1a in NL neurons, suggesting that FMRP may affect dendritic protein synthesis by modulating a subset of translational regulatory machinery. Although a direct link between FMRP and eEF1a and eEF2 mRNAs has not been demonstrated, both of these two elongation factors have been associated with potential roles in cellular growth/proliferation and signal transduction (Lin, Yakymovych, Jia, Yakymovych, & Souchelnytskyi, ; Morrissey et al, ) as well as synaptic regulation (Becker, Kuhse, & Kirsch, ; Mateyak & Kinzy, ; Rosenblum, Meiri, & Dudai, ). In particular, eEF2 has recently been considered as a biochemical sensor that couples neuronal transmission to spine plasticity, a major proposed function of FMRP signaling (Verpelli et al, ).…”

SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity

“…Several studies however, have exposed protein interaction partners that provide clues as to the mechanism of normal SAMHD1 degradation. SAMHD1 interaction with both cyclin L2 and eukaryotic elongation faction 1A1 (eEF1A1) facilitates recruitment to the ubiquitin ligase machinery and subsequent proteosomal degradation (113, 114). A more recent study suggests that interaction with the transmembrane tetraspanin CD81 promotes proteosomal turnover of SAMHD1 (115).…”