DAXX AND DEATH RECEPTOR SIGNALING

DAXX 和死亡受体信号传导

• 批准号: 6740112
• 负责人: Xiaolu Yang
• 金额: $ 24.96万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-03 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740112
• 关键词: CD95 molecule; JUN kinase; apoptosis; biological signal transduction; cell cycle; cytokine receptors; embryonic stem cell; endopeptidases; enzyme activity; intracellular transport; protein protein interaction; protein structure function; protein transport; receptor expression; transport proteins; tumor necrosis factor alpha; tumor suppressor proteins

DESCRIPTION: Apoptosis or programmed cell death is a process of cell auto-destruction that eliminates unwanted, severely damaged, or potentially harmful cells. Apoptosis mediated by a group of cell surface proteins known as the death receptors plays important roles in the regulation of immune responses and immune surveillance of tumor. These receptors include tumor necrosis factor receptor 1 (TNFR1), Fas, death receptor (DR) 3 to 5. Both defective and excessive death receptor signaling cause human disease, ranging from autoimmune disorders to diabetes, hepatitis, and cancer. We have identified Daxx, a novel Fas signaling protein. Daxx induces apoptosis through activation of the c-Jun N-terminal kinase (JNK) pathway; and it directly binds to and activates an apex kinase of the JNK pathway, ASK1. Daxx is predominantly present in distinct subnuclear structures known as nuclear bodies (NBs) or nuclear domain 10 (ND 10). A few other apoptosis proteins, including the tumor suppressor protein PML, are also located at thhe NBs. We propose to further investigate the role of Daxx in death receptor signaling and apoptosis. Specifically, we will determine the involvement of Daxx in the signaling of the other death receptors and the mechanisms by which Daxx activates cell death. These studies should further our understanding of apoptosis regulation and lead to the new effective therapeutic approaches to treat related diseases.

描述：细胞凋亡或程序性细胞死亡是细胞的一个过程 自动销毁，消除不需要的、严重损坏的或潜在的 有害细胞。由一组细胞表面蛋白介导的细胞凋亡 死亡受体在免疫反应的调节中发挥重要作用 和肿瘤的免疫监视。这些受体包括肿瘤坏死因子 受体 1 (TNFR1)、Fas、死亡受体 (DR) 3 至 5。有缺陷和 过度的死亡受体信号传导会导致人类疾病，包括自身免疫性疾病 糖尿病、肝炎和癌症等疾病。我们已经确定了Daxx，一本小说 Fas 信号蛋白。 Daxx 通过激活 c-Jun 诱导细胞凋亡 N-末端激酶（JNK）通路；它直接结合并激活顶点 JNK 通路激酶 ASK1。 Daxx 主要存在于不同的 亚核结构称为核体 (NB) 或核结构域 10 (ND 10）。一些其他凋亡蛋白，包括肿瘤抑制蛋白 PML 也位于 NB。我们建议进一步研究其作用 Daxx 在死亡受体信号传导和细胞凋亡中的作用。具体来说，我们将 确定 Daxx 参与其他死亡受体信号传导 以及 Daxx 激活细胞死亡的机制。这些研究应该 进一步加深我们对细胞凋亡调控的理解，并产生新的有效的 治疗相关疾病的治疗方法。