Human and viral Golgi anti-apoptotic protein (GAAP); a structural and functional study of its mechanism of action

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The life or death of a cell is very strictly regulated and is an essential component in the life of multicellular organisms, including humans. Programmed cell death, called apoptosis, is critical in many processes. For instance, during development, many cells must die to create properly formed organ structures. Cell death also occurs throughout an organism?s life and is crucial to eliminate cells that are functioning incorrectly, including cancer cells or cells infected by a virus. We discovered a new human protein, termed h-GAAP, which controls cell death and that has been conserved during evolution all the way from plants to humans and poxviruses. We studied h-GAAP because vaccinia virus, the vaccine used to eradicate smallpox, makes a very similar protein called v-GAAP.We intend to determine the structure of h-GAAP and v-GAAP, and identify the parts of GAAPs that are needed to i) direct it to its particular location within the cell called the Golgi complex, ii) mediate its interaction with a cell protein called IP3R that regulates calcium and iii) protect cells from apoptosis. The location of h-GAAP in the Golgi complex is particularly interesting because the Golgi is not often associated with the control of cell death. It is important to increase our understanding of this important protein, because h-GAAP is likely to have a role in development, cancer and infectious diseases. We will also study the role of v-GAAP during vaccinia virus infection and compare the role of v-GAAP and other vaccinia virus proteins that inhibit apoptosis.