CORE 2 DB3: CASPASE-DRIVEN HEMATOPOETIC CELL DIFFERENTIATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Driving Biological Project 3: Caspase-driven Hematopoetic Cell Differentiation A new and exciting development in the field of lymphocyte physiology is the finding that caspases, in addition to their role in mediating cell death, also play a critical and positive role in T cell activation and proliferation. Activation of some caspases can be detected early after T cell activation and some caspase substrates are cleaved in the absence of any signs of cell death. Caspases have also been shown to be required for T-cell activation. A familial human immunodeficiency was discovered to be caused by an inactivating mutation in the gene for caspase-8. Taken together, these data allow us to raise the hypothesis that caspases play a permissive role in T lymphocyte physiology presumably by proteolytic processing of a number of cellular proteins, and this will be tested in the project