Functions of Bcl-2 Related Proteins in Activated T Cell Death

Bcl-2相关蛋白在活化T细胞死亡中的功能

• 批准号: 8311793
• 负责人: Philippa C. Marrack
• 金额: $ 24.97万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8311793
• 关键词: Affect; Animals; Antigens; Apoptosis; Apoptotic; Autoimmunity; B-Lymphocytes; Binding; Cause of Death; Cell Death; Cells; Cessation of life; Event; Family; Goals; Half-Life; Homeostasis; Life; Lymphocyte; Measurement; Process; Protein Family; Proteins; Relative (related person); Rest; Risk; Role; Running; Signal Transduction; T-Lymphocyte; Testing; Viral; analog; autoreactive B cell; bak protein; cell killing; cell type; follow-up; interest; killings; lymphoid neoplasm; member; pro-apoptotic protein; programs; research study; response

After encounter with antigen in animals most activated T cells die rapidly. This event relieves the animal of the burden of excess lymphocytes and reduces the risk to the animal of autoimmunity and lymphoid tumors. The death of these cells is known to involve proteins related to Bcl-2, however, the way in which these proteins interact and cause the cells to die is not known. Likewise, anergic B cells also have a shortened half life and recent experiments that this phenomenon also involves members of the Bcl-2 family. Experiments in Project 3 will investigate these problems by studying the changes in amount of, and interactions between, members of the Bcl-2 family of proteins as T cells convert from resting, long lived, to activated, rapidly dying, cells and in anergic B cells. Many of the experiments will focus on Bim, a protein which is very important in signaling lymphocytes to die, however, studies will also be performed to find out what substitutes for Bim when it is absent. In addition, viral analogs of the anti-apoptotic Bcl-2-like proteins will be studied, since one of these proteins, though active in T cells, does not seem to be able to bind Bim in the same way as Bcl-2 does. Moreover, these viral analogs act differently in T and B cells, therefore experiments on their action may reveal important differences between the ways T and B cells die. Finally, it is generally agreed that lymphocytes are actually killed by the Executioner proteins, Bak and Bax. These proteins are thought to be triggered by other pro-apoptotic proteins such as Bim. However, the means whereby Bim delivers the signal to kill to Bak and Bax is not known in spite of many years of study. This Project will follow up the idea that Bim triggers Bak and Bax via a "hit and run" process, with mutational and structural studies on the Executioners and Bim.

在动物体内与抗原接触后，大多数活化的T细胞迅速死亡。这件事减轻了动物的痛苦