BIOL 6 |
| Apoptosis, or programmed cell death, represents an ultimate fate decision in cell biology. This process is critical for cellular differentiation and remodeling of tissues, and for anti-viral and anti-tumor defense. A distinct molecular feature of apoptosis is the widespread but controlled cellular proteolysis, that is predominantly mediated by the caspase family of cysteine proteases. The study of apoptotic pathways has important ramifications for determining what is critical for cellular homeostasis, and for the development of potential anti-cancer therapeutics. We have developed a robust proteomic method for global profiling of proteolysis (“degradomics”) in cells. Key to this is a new method that permits selective labeling and enrichment for the protein N-termini created as a result of proteolysis. Using this approach we have already identified >250 caspase substrates from Jurkat cells that were induced to undergo apoptosis by treatment with the chemotherapeutic agent etoposide. More than 80% of these proteins have not been reported before. These proteins fall into a wide range of functional classes, and reveal much about the molecular components, logic, and timed sequence of events that drive a cell from life to death. We believe this approach will be useful for following the proteolysis of apoptosis induced by various agents or in different cell types, and will be generally useful for dissecting protease signaling pathways. |
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Chemical Approaches to Protein Function
2:00 PM-4:40 PM, Sunday, August 19, 2007 BCEC -- 109A, Oral
Division of Biological Chemistry |