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

果蝇是研究复杂多细胞生物体发育过程中细胞增殖调控的分子机制的理想系统。与所有其他生物一样，大多数果蝇组织中的终末分化之前是G1/0期的细胞周期停滞。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逮捕是依赖于细胞周期蛋白E/Cdk 2（Cdc 2c）和Cdk 1（Cdc 2）复合物的及时失活。在最后的细胞分裂周期中，一方面细胞周期蛋白E（CycE）表达下调，另一方面dacapo（dap）以及fizzy相关（fzr）表达上调。CIP/KIP相关蛋白Dacapo（DAP）抑制细胞周期蛋白E/Cdk 2复合物; FZR蛋白诱导Cdk 1活化细胞周期蛋白A、B和B3降解。哪些机制负责CycE，dap和fzr表达的精确定时变化？目前的知识表明参与细胞周期蛋白D/Cdk 4/6复合物。因此，我们的项目旨在阐明细胞周期蛋白D/Cdk 4/6复合物的作用，特别是在表皮细胞增殖的终止，以及更普遍的生长和增殖在果蝇发育。我们将研究遗传性Cdk 4/6失活和细胞周期蛋白D/Cdk 4/6过表达导致的表型，并鉴定与Cdk 4/6相互作用的基因。

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.