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Mammalian cells have developed effective response mechanisms to survive a wide range of environmental stresses. Among those response mechanisms, post-translational modifications (PTMs) appear to constitute critical mediators required for cell survival during stress. Remarkably, the activity of the most critical PTMs appear to be dramatically enhanced under stress. However, little is known about the mechanism underlying the increases observed. While transcriptional regulation plays an essential role in modulating overall gene expression in mammalian cells, our current knowledge indicates that transcriptional regulatory mechanisms appear to play a very limited role in regulating the activity of most PTM systems in the cell. These findings suggest a role for post-transcriptional regulatory mechanisms as the main modulators of the activity of PTM systems in the cell. One of the most important post-transcriptional mechanisms for controlling gene expression is alternative splicing. Alternatively spliced gene transcripts may lead to complex feedback mechanisms that can have profound effects in their expression. Through polyribosome profiling and quantitative PCR, we have demonstrated that the transcript for one important post-translational protein modifier undergoes alternative splicing and is therefore likely to produce alternative gene products that could modulate various processes in the cell and demonstrate cell line specificity. Such gene products may be differentially regulated, thus playing unique roles in the cellular stress response. Enhancing our understanding of these critical mechanisms could lead to the development of novel therapies for illnesses that cause cellular stress such as viral infection and stroke.