Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1 |
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Authors: | Jorge Henao-Mejia |
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Institution: | a Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA b Center for AIDS Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA |
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Abstract: | Sam68 has been implicated in a variety of important cellular processes such as RNA metabolism and intracellular signaling. We have recently shown that Sam68 cytoplasmic mutants induce stress granules (SG) and inhibit HIV-1 nef mRNA translation J. Henao-Mejia, Y. Liu, I.W. Park, J. Zhang, J. Sanford, J.J. He, Suppression of HIV-1 Nef translation by Sam68 mutant-induced stress granules and nef mRNA sequestration, Mol. Cell 33 (2009) 87-96]. These findings prompted us to investigate the possibility and the underlying mechanisms of the wild-type counterpart Sam68 SG recruitment. Herein, we revealed that Sam68 was significantly recruited into cytoplasmic SG under oxidative stress. We then demonstrated that domain aa269-321 and KH domain were both essential for this recruitment. Nevertheless, Sam68 knockdown had no effects on SG assembly, indicating that Sam68 is not a constitutive component of the SG. Moreover, we showed that Sam68 cytoplasmic mutant-induced SG formation was independent of eIF2α phosphorylation. Lastly, we demonstrated that Sam68 was complexed with T-cell intracellular antigen-1 (TIA-1), a core SG component, and that the complex formation was correlated with Sam68 SG recruitment. Taken together, these results provide direct evidence for the first time that Sam68 is recruited into SG through complexing with TIA-1 in response to oxidative stress and suggest that cytoplasmic SG recruitment of Sam68 and ensuing changes in Sam68 physiological functions are part of the host response to external stressful conditions. |
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Keywords: | eIF2α eukaryotic elongation factor 2α G3BP Ras-GTPase-activating protein SH3 domain-binding protein 1 hnRNP A1 heteronuclear ribonucleoprotein A1 KH heteronuclear ribonucleoprotein particle K homology domain PABP poly(A)-binding protein PB processing bodies RBP RNA-binding proteins Sam68 Src-associated protein in mitosis SG stress granules TIA-1 T-cell intracellular antigen-1 |
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