Cytoskeleton polymerization dynamics in the cell cycle

细胞周期中的细胞骨架聚合动力学

• 批准号: 7817669
• 负责人: Timothy J Mitchison
• 金额: $ 34.08万
• 依托单位: HARVARD MEDICAL SCHOOL
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7817669
• 关键词: Affinity; Amino Acids; Antibodies; Antineoplastic Agents; Apoptosis; Biochemical; Biochemistry; Biological; Biological Markers; Cancer Patient; Cataloging; Catalogs; Cell Culture Techniques; Cell Cycle; Cell Surface Proteins; Cell division; Cell membrane; Cell surface; Cells; Chemotherapy-Oncologic Procedure; Classification; Cultured Cells; Cytokinesis; Cytoplasm; Cytoskeleton; Data; Development; Drug usage; Extracellular Matrix; Human; Image; Interphase; Label; Learning; Life; Malignant Neoplasms; Mammalian Cell; Mass Spectrum Analysis; Membrane; Membrane Proteins; Methods; Mitosis; Mitotic; Modification; Monoclonal Antibodies; Mus; Paclitaxel; Pharmaceutical Preparations; Post-Translational Protein Processing; Proteins; Proteomics; Protocols documentation; Reagent; Research; Resistance; Stable Isotope Labeling; Surface; Tissues; Tumor Tissue; Work; cancer cell; cancer therapy; combat; comparative; improved; novel; polymerization; public health relevance; response; tumor

DESCRIPTION (provided by applicant): We will generate a catalog of biochemical changes that occur on the surface of cancer during cell division (mitosis and cytokinesis) and during programmed cell death (apoptosis). We will obtain these data by labeling the surface of cultured cells that have been synchronized using drugs, isolating plasma membrane proteins, and then comparing different cell states by a quantitative, comparative mass spectrometry method called SILAC. Our catalog will allow us to identify cell-surface biomarkers for mitotic arrest and apoptosis, and we will generate antibodies that recognize these biomarkers. These biomarkers will be very useful for understanding why some cancers are resistant to anti-mitotic cancer drugs such as paclitaxel, and learning how to combat that resistance. Our catalog will also open new avenues in cell cycle research, since there have been no systematic studies of how the cell cycle regulates the cell surface since the 1970s. PUBLIC HEALTH RELEVANCE: We will use mass spectrometry to discover proteins or protein modifications on the cell surface that are selective for dividing or dying cells. These will provide biomarkers for understanding how anti-mitotic drugs work or fail in cancer therapy, as well as opening new avenues in cell cycle research.

描述（由申请人提供）：我们将生成细胞分裂（有丝分裂和胞质分裂）和程序性细胞死亡（细胞凋亡）期间癌症表面发生的生化变化目录。我们将通过标记已使用药物同步的培养细胞表面，分离质膜蛋白，然后通过称为SILAC的定量比较质谱法比较不同细胞状态来获得这些数据。我们的目录将使我们能够识别有丝分裂停滞和凋亡的细胞表面生物标志物，我们将产生识别这些生物标志物的抗体。这些生物标志物对于理解为什么一些癌症对抗有丝分裂癌症药物（如紫杉醇）具有耐药性以及学习如何对抗这种耐药性非常有用。我们的目录还将为细胞周期研究开辟新的途径，因为自20世纪70年代以来，还没有对细胞周期如何调节细胞表面进行系统研究。 公共卫生相关性：我们将使用质谱法来发现细胞表面的蛋白质或蛋白质修饰，这些蛋白质或蛋白质修饰对分裂或死亡细胞具有选择性。这些将为了解抗有丝分裂药物在癌症治疗中如何起作用或失败提供生物标志物，并为细胞周期研究开辟新途径。