TY - JOUR
T1 - Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1
AU - Henao-Mejia, Jorge
AU - He, Johnny J.
N1 - Funding Information:
We thank Dr. Janice Blum, Dr. Ann Roman, Dr. Jeremy Sanford and Dr. Ronald Wek for advices. We also thank Dr. Sonia Guil and Dr. Javier Caceres for GFP.TIA-1, GFP.hnRNP A1, GFP.PABP, and GFP.G3BP plasmids. This work was supported by the grants R01NS039804 and R01NS065785 (to JJH) from the National Institutes of Health.
PY - 2009/11/15
Y1 - 2009/11/15
N2 - 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.
AB - 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.
KW - Oxidative stress
KW - Relocalization
KW - Sam68
KW - Stress granules
KW - Stress response
KW - TIA-1 binding
UR - http://www.scopus.com/inward/record.url?scp=70350380472&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2009.07.011
DO - 10.1016/j.yexcr.2009.07.011
M3 - Article
C2 - 19615357
AN - SCOPUS:70350380472
SN - 0014-4827
VL - 315
SP - 3381
EP - 3395
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 19
ER -