mTor Is a signaling hub in cell survival: A mass-spectrometry-based proteomics investigation
Baykal, Ahmet Tarık
Quezada, Hernan Concha
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CitationTang, Z., Baykal, A. T., Gao, H., Quezada, H. C., Zhang, H., Bereczki, E. ... Pei, J.-J. (2014). mTor Is a signaling hub in cell survival: A mass-spectrometry-based proteomics investigation. Journal of Proteome Research, 13(5), 2433-2444. https://dx.doi.org/10.1021/pr500192g
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.