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

细胞的生死受到非常严格的调控，是包括人类在内的多细胞生物生命的重要组成部分。程序性细胞死亡，称为细胞凋亡，在许多过程中至关重要。例如，在发育过程中，许多细胞必须死亡才能形成正确的器官结构。细胞死亡也发生在整个生物体中？它对消除功能不正常的细胞至关重要，包括癌细胞或被病毒感染的细胞。我们发现了一种新的人类蛋白质，称为h-GAAP，它控制细胞死亡，并且在从植物到人类和痘病毒的进化过程中一直保守。我们研究h-GAAP是因为用于根除天花的疫苗牛痘病毒产生一种非常相似的蛋白质，称为v-GAAP。我们打算确定h-GAAP和v-GAAP的结构，并确定GAAP的部分，这些部分需要i）将其引导到细胞内称为高尔基复合体的特定位置，ii）介导其与调节钙的称为IP 3R的细胞蛋白的相互作用，和iii）保护细胞免于凋亡。h-GAAP在高尔基复合体中的位置特别有趣，因为高尔基体通常不与细胞死亡的控制相关。重要的是增加我们对这种重要蛋白质的理解，因为h-GAAP可能在发育，癌症和传染病中发挥作用。我们还将研究v-GAAP在牛痘病毒感染过程中的作用，并比较v-GAAP和其他抑制细胞凋亡的牛痘病毒蛋白的作用。

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.