mTor is a signaling hub in cell survival: a mass-spectrometry-based proteomics investigation.
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-SY5Y cells expressing genetically modified mTor. Cell death in SH-SY5Y 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.
KI-Alzheimer Disease Research Center, Karolinska Institutet , SE 14186 Huddinge, Sweden.
Zhi
Z
Tang
Ahmet Tarik
AT
Baykal
Hui
H
Gao
Hernan Concha
HC
Quezada
Haiyan
H
Zhang
Erika
E
Bereczki
Muge
M
Serhatli
Betul
B
Baykal
Cigdem
C
Acioglu
Shan
S
Wang
Eniko
E
Ioja
Xinying
X
Ji
Yan
Y
Zhang
Zhizhong
Z
Guan
Bengt
B
Winblad
Jin-Jing
JJ
Pei
D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D008928:Mitochondria / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D016875:tau Proteins / Q000378:metabolism
D046912:Multiprotein Complexes; D011506:Proteins; D016875:tau Proteins; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases; D020169:Caspases