The function of the Cyclin D-dependent protein kinase Cdk4/6 in Drosophila Die Funktion der Cyclin D-abhängigen Proteinkinase Cdk4/6 in Drosophila

细胞周期蛋白 D 依赖性蛋白激酶 Cdk4/6 在果蝇中的功能

• 批准号: 5225012
• 负责人: Professor Dr. Christian F. Lehner
• 金额: --
• 依托单位: Institute of Molecular Life Sciences
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1995
• 资助国家: 德国
• 起止时间: 1994-12-31 至 2001-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5225012?language=en
• 关键词: function; Cyclin; dependent; protein; kinase

Drosophila is an ideal system for the in vivo analysis of the molecular mechanisms which regulate the extensive cell proliferation during development of complex multicellular organisms. As in essentially all other organisms, terminal differentiation is preceded by a cell cycle arrest during a G1/0 phase in most Drosophila tissues. In the epidermis, where cell proliferation is stopped after the sixteenth round of cell division, we have been able to demonstrate that this arrest is dependent on the timely inactivation of Cyclin E/Cdk2(Cdc2c)- and Cdk1(Cdc2)complexes. During the final cell division cycle, Cyclin E (CycE) expression is down-regulated, on the one hand, and dacapo(dap)- as well as fizzy-related(fzr)-expression are up-regulated on the other hand. The CIP/KIP-related protein Dacapo(DAP) inhibits Cyclin E/Cdk2-complexes; FZR-protein induces the degradation of the Cdk1-activating Cyclins A, B and B3. Which mechanisms are responsible for the precisely timed changes of CycE, dap and fzr expression? Current knowledge would suggest an involvement of Cyclin D/Cdk4/6-complexes. Thus, our project aims at an elucidation of the role of Cyclin D/Cdk4/6complexes specifically during the termination of the epidermal cell proliferation as well as more generally during growth and proliferation in Drosophila development. We will characterise phenotypes resulting from genetic Cdk4/6-inactivation and Cyclin D/Cdk4/6 overexpression, and we will identify genes interacting with Cdk4/6.

果蝇是研究复杂多细胞生物发育过程中调控广泛细胞增殖的分子机制的理想系统。和所有其他生物一样，在大多数果蝇组织中，在G1/0期的细胞周期阻滞发生在终末分化之前。在表皮中，细胞增殖在第十六轮细胞分裂后停止，我们已经能够证明这种停止依赖于细胞周期蛋白E/Cdk2(Cdc2c)-和Cdk1（Cdc2）复合物的及时失活。在细胞最后的分裂周期中，Cyclin E （CycE）表达下调，dacapo(dap)-以及fizzy-related(fzr)-表达上调。CIP/ kip相关蛋白Dacapo（DAP）抑制Cyclin E/ cdk2复合物；fzr蛋白诱导cdk1激活细胞周期蛋白A、B和B3的降解。哪些机制导致CycE、dap和fzr表达的精确定时变化？目前的知识表明与细胞周期蛋白D/ cdk4 /6复合物有关。因此，我们的项目旨在阐明Cyclin D/ cdk4 /6复合物在表皮细胞增殖终止过程中的作用，以及在果蝇发育过程中更普遍的生长和增殖过程。我们将描述由遗传Cdk4/6失活和细胞周期蛋白D/Cdk4/6过表达引起的表型，我们将确定与Cdk4/6相互作用的基因。