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Published January 1, 2014 | Version v1
Journal article Open

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

Creators

  • 1. Karolinska Inst, KI Alzheimer Dis Res Ctr, SE-14186 Huddinge, Sweden
  • 2. Istanbul Medipol Univ, Sch Med, Dept Med Biochem, TR-34083 Unkapani, Fatih Istanbul, Turkey
  • 3. Karolinska Inst, Dept Biosci & Nutr, SE-14157 Huddinge, Sweden
  • 4. Karolinska Inst Hosp, Ctr Infect Med, Dept Med, Huddinge, Sweden
  • 5. TUBITAK, Marmara Res Ctr, Genet Engn & Biotechnol Inst, TR-41470 Gebze, Turkey
  • 6. Henan Univ, Sch Med, Inst Immunol, Henan Prov Key Med Lab Cellular & Mol Immunol, Kaifeng 475004, Henan, Peoples R China

Description

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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