We used an untargeted pro-24 teomic approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify 25 and characterize time-series proteome-wide changes in dose-responsive mild and extreme proteo-26 toxic stress models in medulloblastoma [Daoy], neuroblastoma [SH-SY5Y] and differentiated SH-27 SY5Y neuronal cells. Combined global analysis of condition-time point datasets identified 1010 dif-28 ferentially expressed proteins (DEPs) in Daoy cells, 623 in SH-SY5Y cells, and 365 in differentiated 29 SH-SY5Y cells. The condition-specific analysis presents more DEPs and upregulated proteins in ex-30 treme heat stress with a relatively conservative and tight regulation in differentiated SH-SY5Y neu-31 ronal cells. Functional network analysis using ingenuity pathway analysis (IPA) identified path-32 ways associated with biological processes of protein, RNA, and amino acid metabolism, cellular 33 response to stress, and membrane trafficking as common to the three cell types.