Isoform-Specific Analysis of Accelerated Cellular Senescence and Escape with High-throughput Top Down Proteomics

摘要

Originally thought to be a laboratory curiosity, research has shown several phenotypes related to senescence to be important in understanding mechanisms of aging and responses to cancer treatment. Of these, accelerated senescence resulting from chemotherapy has been shown to lead to a dormant cell state and a low probability of escape in cells such as the p53-null non-small cell lung carcinoma line, H1299. However, the proteomic changes occurring in this model are not well studied. Recent advances in workflows for high-throughput Top Down Proteomics have allowed proteome coverage over a larger mass range than previously possible. This platform allows identification and quantitation of protein species arising from combinations of post-translational modifications (PTMs) in a gene-specific fashion.