Role of dre-1/FBXO11 in apoptosis

dre-1/FBXO11 在细胞凋亡中的作用

• 批准号: 7808244
• 负责人: Michael Chiorazzi
• 金额: $ 4.62万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7808244
• 关键词: Aging; Animal Model; Animals; Apoptosis; Apoptotic; Autoimmune Diseases; Biochemical; Biological Assay; Biology; Birth; Caenorhabditis elegans; Cancer Etiology; Cancerous; Caspase Inhibitor; Cell Death; Cell Line; Cell Survival; Cells; Cessation of life; Collaborations; Decision Making; Defect; Development; Ectopic Expression; Embryonic Development; Figs - dietary; Genes; Genetic; Genetic Screening; Goals; Homologous Gene; Human; Immune; Infection; Life; Ligase; Lymphoma; Malignant Neoplasms; Metabolism; Minor; Modeling; Molecular; Mutation; National Cancer Institute; Nematoda; Nerve Degeneration; Organism; Pathogenesis; Premature aging syndrome; Process; Proteins; Regulation; Research Project Grants; Role; System; Tail; Testing; Time; Tumor Suppressor Proteins; Ubiquitin-mediated Proteolysis Pathway; Work; accomplished suicide; base; cancer therapy; cell suicide; fighting; human disease; improved; large cell Diffuse non-Hodgkin' s lymphoma; mature animal; multicatalytic endopeptidase complex; mutant; novel; null mutation; prevent; programs; protein degradation; research study; ubiquitin-protein ligase

DESCRIPTION (provided by applicant): The precise control of apoptosis is vital to the survival of an organism. If this process is improperly regulated, developmental defects, cancer, neurodegeneration and premature aging can result. The molecular mechanisms for apoptotic regulation are remarkably well-conserved in function and sequence across the animal kingdom, and studies in model organisms have provided an immense amount of information relevant to human diseases related to cell death. I have uncovered a novel role for a conserved gene, dre-1/FBXO11, in controlling apoptosis in the nematode Caenorhabditis elegans. We have reason to suspect that this gene is important for the pathogenesis of human lymphoma. My thesis research project will involve investigating the mechanism of dre-1/FBXO11 action in the hope of improving our understanding of apoptotic regulation. A surprising fact in biology is that many cells in humans and other organisms make the decision to commit suicide. This is a normal process that helps produce a properly-developed organism at birth, helps prevent abnormal pre-cancerous cells from growing out of control, and helps produce immune cells that can fight infection. We would like to better understand how this decision is made in order to develop better treatments for cancer and autoimmune disease (in which cells do not die when they should) and neurodegeneration and aging (in which cells are lost that should survive).

描述（由申请人提供）：细胞凋亡的精确控制对生物体的生存至关重要。如果这一过程调节不当，就会导致发育缺陷、癌症、神经变性和早衰。凋亡调控的分子机制在整个动物王国中在功能和序列上都非常保守，对模式生物的研究提供了与细胞死亡相关的人类疾病相关的大量信息。我发现了一个保守基因，dre-1/FBXO11，在控制秀丽隐杆线虫细胞凋亡中的新作用。我们有理由怀疑这个基因对人类淋巴瘤的发病机制很重要。我的论文研究项目将涉及研究dre-1/FBXO11的作用机制，希望能提高我们对细胞凋亡调控的认识。生物学中一个令人惊讶的事实是，人类和其他生物体中的许多细胞都会做出自杀的决定。这是一个正常的过程，有助于在出生时产生发育良好的生物体，有助于防止异常的癌前细胞失控生长，并有助于产生可以抵抗感染的免疫细胞。我们希望更好地了解这个决定是如何做出的，以便开发出更好的治疗癌症和自身免疫性疾病（其中细胞在应该死亡的时候没有死亡）以及神经变性和衰老（其中应该存活的细胞丢失）的方法。