AR COBRE: PROTEIN INTERACTIONS IN CARCINOGENESIS AND CANCER TREATMENT

AR COBRE：致癌和癌症治疗中的蛋白质相互作用

• 批准号: 7959347
• 负责人: Yuchun Du
• 金额: $ 28.83万
• 依托单位: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959347
• 关键词: Apoptosis; Apoptotic; Bax protein; Biochemical Pathway; C-terminal; Cell Death; Cells; Centers of Research Excellence; Computer Retrieval of Information on Scientific Projects Database; Cytosol; Data; Development; Disease; Family; Functional disorder; Funding; Grant; Homeostasis; Human Development; Institution; Malignant Neoplasms; Mediating; Membrane Potentials; Mitochondria; Molecular Conformation; Molecular Weight; Organism; Outer Mitochondrial Membrane; Pathway interactions; Protein Family; Proteins; Research; Research Personnel; Resources; Source; Tissues; United States National Institutes of Health; cancer therapy; carcinogenesis; mitochondrial membrane; pro-apoptotic protein; protein complex; protein structure function; treatment center

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. Apoptosis, or programmed cell death, is a biochemical pathway critical to normal development and tissue homeostasis in multi-cellular organisms. Dysfunction of apoptosis results in development of human cancer and other diseases. The Bcl-2 family of proteins constitutes a crucial checkpoint in the apoptosis pathway. Bax is one of the two key proteins (Bax and Bak) of the Bcl-2 family that control the mitochondrion-mediated cell death pathway. In normal healthy cells, Bax locates in the cytosol and is maintained in the inactive state. Upon apoptotic stimulation, Bax undergoes conformational changes, and migrates from the cytosol to mitochondria. By insertion of its hydrophobic C-terminal end to the mitochondrial outer membrane, Bax disrupts mitochondrial membrane potential, and induces the release of pro-apoptotic proteins from mitochondria, which in turn triggers apoptosis. What maintains Bax in its inactive conformation in the cytosol of healthy cells, and what factors trigger the conformational changes of Bax upon apoptotic stimulation remain unclear. Our preliminary data showed that in addition to the majority of monomeric Bax, a small portion of Bax was associated with high molecular weight protein complexes in the cytosol of healthy cells. We hypothesize that the proteins that associate with Bax in healthy or apoptotic cells hold the key to Bax activation in apoptosis.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 细胞凋亡或程序性细胞死亡是对多细胞生物体的正常发育和组织稳态至关重要的生化途径。细胞凋亡功能障碍导致人类癌症和其他疾病的发生。 Bcl-2 蛋白家族构成细胞凋亡途径中的关键检查点。 Bax 是 Bcl-2 家族的两个关键蛋白（Bax 和 Bak）之一，控制线粒体介导的细胞死亡途径。在正常健康细胞中，Bax 位于细胞质中并保持非活性状态。 在细胞凋亡刺激下，Bax 发生构象变化，并从细胞质迁移到线粒体。通过将其疏水性 C 末端插入线粒体外膜，Bax 会破坏线粒体膜电位，并诱导线粒体释放促凋亡蛋白，从而引发细胞凋亡。是什么使 Bax 在健康细胞的细胞质中保持非活性构象，以及哪些因素在凋亡刺激后触发 Bax 的构象变化仍不清楚。我们的初步数据表明，除了大部分单体 Bax 外，一小部分 Bax 与健康细胞胞浆中的高分子量蛋白质复合物相关。我们假设健康或凋亡细胞中与 Bax 相关的蛋白质掌握着凋亡中 Bax 激活的关键。