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

Tang Z., Baykal A. T., Gao H., Quezada H. C., Zhang H., Bereczki E., ...Daha Fazla

JOURNAL OF PROTEOME RESEARCH, cilt.13, sa.5, ss.2433-2444, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 13 Sayı: 5
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1021/pr500192g
  • Dergi Adı: JOURNAL OF PROTEOME RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.2433-2444
  • Anahtar Kelimeler: mTor, cell survival, apoptosis, caspases, mitochondria, SH-SY5Y NEUROBLASTOMA-CELLS, CYCLIN-DEPENDENT KINASE-5, ALZHEIMER-DISEASE BRAIN, P70 S6 KINASE, NEUROFIBRILLARY PATHOLOGY, PROTEIN-KINASES, TAU-PHOSPHORYLATION, STATISTICAL-MODEL, MAMMALIAN TARGET, UP-REGULATION
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

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.