Napolitano Giuliana, Majello Barbara, Lania Luigi
Department of Genetics, Molecular and General Biology, University of Naples Federico II, 80134 Naples, Italy.
Int J Oncol. 2002 Jul;21(1):171-7.
Cell division and proliferation of all eukaryotics must follow a genetic program, termed the cell cycle. To ensure proper progression through the cell cycle, proteins that are intimately involved in its regulation must be periodically expressed within an appropriate window of the cycle. Cyclin and cyclin-dependent kinases are the modular components of the core clock machinery of the cell cycle. Progression through the cell cycle requires the activation of Cdks. The activities of these classes of kinases are tightly regulated by both positive and negative factors, and most importantly perturbation of Cdk activities can result in tumorigenesis. Progress has been made recently in connecting specific cyclin-Cdk kinase complexes and transcription. It is still unclear how cyclin/Cdk complexes regulate transcription, and most importantly what their substrates are. The aim of this review is to discuss our current understanding of the molecular mechanisms underlying the transcription properties of defined cyclin-dependent kinases, with a particular emphasis on the cyclin T/Cdk9 (P-TEFb) complex, and its role in the regulation of cell cycle controlling genes.
所有真核生物的细胞分裂和增殖都必须遵循一个称为细胞周期的遗传程序。为确保细胞周期的正常进行，密切参与其调控的蛋白质必须在细胞周期的适当时间窗口内周期性表达。细胞周期蛋白和细胞周期蛋白依赖性激酶是细胞周期核心时钟机制的模块化组成部分。细胞周期的进行需要细胞周期蛋白依赖性激酶（Cdks）的激活。这些激酶类别的活性受到正性和负性因子的严格调控，最重要的是，细胞周期蛋白依赖性激酶活性的紊乱会导致肿瘤发生。最近在将特定的细胞周期蛋白 - Cdk激酶复合物与转录联系起来方面取得了进展。目前仍不清楚细胞周期蛋白/Cdk复合物如何调节转录，最重要的是它们的底物是什么。本综述的目的是讨论我们目前对特定细胞周期蛋白依赖性激酶转录特性的分子机制的理解，特别强调细胞周期蛋白T/Cdk9（P-TEFb）复合物及其在调控细胞周期控制基因中的作用。
