RT Journal Article SR Electronic T1 Time-resolved proteomics vs. ribosome profiling reveals translation dynamics under stress JF bioRxiv FD Cold Spring Harbor Laboratory SP 087486 DO 10.1101/087486 A1 Tzu-Yu Liu A1 Hector H. Huang A1 Diamond Wheeler A1 James A. Wells A1 Yun S. Song A1 Arun P. Wiita YR 2016 UL http://biorxiv.org/content/early/2016/11/14/087486.abstract AB Many small molecule chemotherapeutics induce stresses that globally inhibit mRNA translation, remodeling the cancer proteome and governing response to treatment. Here we measured protein synthesis in multiple myeloma cells treated with low-dose bortezomib by coupling pulsed-SILAC (pSILAC) with high-accuracy targeted quantitative proteomics. We found that direct measurement of protein synthesis by pSILAC correlated well with the indirect measurement of protein synthesis by ribosome profiling under conditions of robust translation. By developing a statistical model integrating longitudinal proteomic and mRNA-seq measurements, we found that proteomics could directly detect global alterations in translational rate as a function of therapy-induced stress after prolonged bortezomib exposure. Finally, the model we develop here, in combination with our experimental data including both protein synthesis and degradation, predicts changes in proteome remodeling under a variety of cellular perturbations. pSILAC therefore provides an important complement to ribosome profiling in directly measuring proteome dynamics under conditions of cellular stress.