F-box proteins: deregulated cell cycle control and proteolysis in cancer

F-box 蛋白：癌症中细胞周期控制和蛋白水解失调

基本信息

批准号：
8761279
负责人：
MICHELE PAGANO
金额：
$ 22.39万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-11-29 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8761279
关键词：
Automobile Driving Basic Science Biochemical Biological Cancer Biology Cell Cycle Cell Cycle Deregulation Cell Cycle Progression Cell Cycle Regulation Cell Survival Cell division Cell physiology Cells Commit Complex Cultured Cells Development Dimensions Ectopic Expression Ensure Event F Box Domain F-Box Motifs F-Box Proteins Family Funding Funding Agency Genetic Growth Human Instruction Knowledge Laboratories Lead Life Link Malignant - descriptor Malignant Neoplasms Methods Mitotic Molecular Mus Oncogene Proteins Pathway interactions Play Process Proteasome Inhibitor Proteolysis Research Role Signal Transduction Somatic Cell System Therapeutic Therapeutic Intervention Translational Research Ubiquitin Ubiquitin-mediated Proteolysis Pathway Work base cancer cell cancer therapy cell growth cell transformation in vivo inhibitor/antagonist interdisciplinary approach mouse model novel outcome forecast overexpression paralogous gene programs research study tissue culture tool tumor tumorigenesis ubiquitin ligase

项目摘要

A detailed understanding of the nnolecular and cellular events influencing the three key dimensions of cellular life (growth/proliferation, survival, and differentiation) remains a central question in cancer biology. Further understanding of the influence of the ubiquitin system on the transformation process will help to identify novel targets for cancer therapy. The first years of work under CA76584 (started in 1998) set the bases for elucidating the role played by F-box proteins in human oncogenesis, which was accomplished during the second funding cycle. In its third cycle, CA76584 is currently devoted to elucidating the integration of the ubiquitin system in the signaling networks of the cell, and its corruption in cancer. In particular, our research program involves the study of the human family of SCF and SCF-like ubiquitin ligases to gain an understanding of the molecular mechanisms through which they control basic cellular processes, such as cell growth, cell division, and cell survival. To this end, we are using a comprehensive and interdisciplinary approach that includes biochemical and biological methods, as well as somatic cell and mouse genetics. These tools, together with our expertise in the ubiquitin system, will ensure that our laboratory will continue to contribute to the understanding of cell functions during the coming years. As the mechanisms of the ubiquitin-mediated proteolysis of cell cycle regulators are unraveled, this team is committed to the integration of its basic research results with an understanding of malignant transformation.

对影响的未分子和细胞事件的详细理解影响了三个关键维度细胞寿命（生长/增殖，生存和分化）仍然是癌症生物学的核心问题。进一步了解泛素系统对转化过程的影响将有助于确定癌症治疗的新靶标。根据CA76584（始建于1998年）的工作的头几年阐明F-box蛋白在人肿瘤发生中起作用的作用的基础，该作用已完成在第二个融资周期中。在第三个周期中，CA76584目前致力于阐明泛素系统在细胞的信号网络中的整合及其在癌症中的腐败。在特别是，我们的研究计划涉及对SCF和类似SCF的泛素家族的研究连接酶以了解它们控制基本细胞的分子机制过程，例如细胞生长，细胞分裂和细胞存活。为此，我们正在使用一个全面的和跨学科方法，包括生化和生物学方法，以及体细胞和小鼠遗传学。这些工具，以及我们在泛素系统中的专业知识，将确保我们的实验室将在未来几年继续为对细胞功能的理解做出贡献。作为泛素介导的细胞周期调节剂的蛋白水解的机制已解散，该团队是致力于将其基础研究结果整合在一起，并了解恶性转化。