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 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞凋亡或程序性细胞死亡是多细胞生物体正常发育和组织稳态的关键生化途径。细胞凋亡的功能障碍导致人类癌症和其他疾病的发展。Bcl-2蛋白家族构成了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质（Bax和巴克）之一，其控制着Bcl-2介导的细胞死亡途径。在正常的健康细胞中，Bax定位于胞浆中并维持在非活性状态。 在凋亡刺激下，Bax经历构象变化，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在健康细胞的胞质溶胶中保持其非活性构象，以及什么因素触发Bax在凋亡刺激后的构象变化仍不清楚。我们的初步数据表明，除了大多数单体Bax，Bax的一小部分与健康细胞的胞质溶胶中的高分子量蛋白质复合物。我们推测，在健康或凋亡细胞中与Bax相关的蛋白质是凋亡中Bax激活的关键。