Cks proteins in cell cycle control and tumorogenesis

Cks 蛋白在细胞周期控制和肿瘤发生中的作用

• 批准号: 7566879
• 负责人: Steven I Reed
• 金额: $ 8.91万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-18 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7566879
• 关键词: Alleles; Area; Binding; Biological Process; Cell Cycle Regulation; Cell Survival; Complex; Cyclin-Dependent Kinases; Cyclins; Development; Disease; Embryo; Eukaryota; Eukaryotic Cell; Fibroblasts; Goals; Human; Investigation; Link; Malignant Neoplasms; Mammalian Cell; Mammals; Modeling; Molecular; Molecular Genetics; Morula; Mus; Phenotype; Phosphotransferases; Protein Overexpression; Protein Subunits; Proteins; Role; Saccharomycetales; Staging; Work; Yeasts; base; carcinogenesis; chromatin remodeling; malignant phenotype; paralogous gene; protective effect; protein function; therapeutic target; tumor; tumor progression; tumorigenesis

Cks (Cdc kinase subunit) proteins were originally identified through their ability to genetically suppress defective alleles of the cyclin-dependent kinases (CDKs) of both fission and budding yeast. Subsequent investigations demonstrated that these small (9-18kD) proteins were ubiquitous in eukaryotes and could directly bind to CDK/cyclin complexes, hence the designation Cks. Humans and other mammals express two Cks paralogs, which are often overexpressed in cancer, which in some cases is associated with aggressive disease and poor survival. Yet neither the precise essential function(s) of these proteins nor their role in oncogenesis have been elucidated. The current proposal aims to use molecular and molecular genetic approaches to determine the essential functions of Cks1 and Cks2 in mammalian cells. Furthermore, the cellular effects of Cks protein overexpression will be explored to elucidate the link to malignancy. Finally, mouse tumor models will be used to determine if partial loss of Cks protein function can be protective against malignancy, potentially validating functional interactions between Cks proteinprotein as therapeutic targets.

CK（CDC激酶亚基）蛋白最初是通过遗传抑制的能力来鉴定的 裂变和发芽酵母的细胞周期蛋白依赖性激酶（CDK）的缺陷等位基因。随后的 调查表明，这些小（9-18KD）蛋白在真核生物中无处不在，可以 直接与CDK/Cyclin复合物结合，因此名称CK。人类和其他哺乳动物表达 两个CKS旁系同源物通常在癌症中过表达，在某些情况下与 侵略性疾病和生存不良。然而，这些蛋白质的确切基本功能也不是 它们在肿瘤发生中的作用已被阐明。当前的建议旨在使用分子和分子 确定CKS1和CKS2在哺乳动物细胞中的基本功能的遗传方法。 此外，将探索CKS蛋白过表达的细胞效应，以阐明与 恶性。最后，小鼠肿瘤模型将用于确定CKS蛋白功能的部分损失是否 可以防止恶性肿瘤，可能验证CKS蛋白质蛋白之间的功能相互作用 作为治疗靶标。