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mTor Is a Signaling Hub in Cell Survival: A Mass-Spectrometry-Based Proteomics Investigation

   Tang, Zhi; Baykal, Ahmet Tank; Gao, Hui; Quezada, Hernan Concha; Zhang, Haiyan; Bereczki, Erika; Serhatli, Muge; Baykal, Betul; Acioglu, Cigdem; Wang, Shan; Ioja, Eniko; Ji, Xinying; Zhang, Yan; Guan, Zhizhong; Winblad, Bengt; Pei, Jin-Jing

mTor plays a central role in controlling protein homeostasis and cell survival. Recently, we have demonstrated that perturbations of mTor signaling are implicated in Alzheimer's disease (AD) and that mTor complex 1 (mTorC1) is involved in the formation of toxic phospho-tau. Therefore, we employed mass-spectrometry-based proteomics to identify specific protein expression changes in relation with cell survival in human neuroblastoma SH-SYSY cells expressing genetically modified mTor. Cell death in SH-SYSY cells was induced by moderate serum deprivation. Using flow cytometry we observed that up-regulated mTor complex 2 (mTorC2) increases the number of viable cells. By using a combination approach of proteomic and enrichment analysis we have identified several proteins (Thioredoxin-dependent peroxide reductase, Peroxiredoxin-5, Cofilin 1 (non-muscle), Annexin A5, Mortalin, and 14-3-3 protein zeta/delta) involved in mitochondrial integrity, apoptotosis, and pro-survival functions (caspase inhibitor activity and anti-apoptosis) that were significantly altered by mTor activity modulation. The major findings of this study are the implication of mTorC2 but not mTorC1 in cell viability modulation by activating the pro-survival machinery. Taken together, these results suggest that up-regulated mTorC2 might be playing an important role in promoting cell survival by suppressing the mitochondria-caspase-apoptotic pathway in vitro.

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