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细胞周期蛋白依赖性激酶7(CDK7)和9(CDK9)在协调转录和细胞周期检查点调控中的作用。

The involvement of cyclin-dependent kinase 7 (CDK7) and 9 (CDK9) in coordinating transcription and cell cycle checkpoint regulation.

作者信息

Lee Cheng-Fan, Pienta Kenneth J, Amend Sarah R

机构信息

Cancer Ecology Center, The Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, USA.

出版信息

Cell Cycle. 2024 Nov-Dec;23(21-24):962-974. doi: 10.1080/15384101.2025.2485844. Epub 2025 Apr 14.

Abstract

Cells regulate the expression of cell cycle-related genes, including cyclins essential for mitosis, through the transcriptional activity of the positive transcription elongation factor b (P-TEFb), a complex comprising CDK9, cyclin T, and transcription factors. P-TEFb cooperates with CDK7 to activate RNA polymerase. In response to DNA stress, the cell cycle shifts from mitosis to repair, triggering cell cycle arrest and the activation of DNA repair genes. This tight coordination between transcription, cell cycle progression, and DNA stress response is crucial for maintaining cellular integrity. Cyclin-dependent kinases CDK7 and CDK9 are central to both transcription and cell cycle regulation. CDK7 functions as the CDK-activating kinase (CAK), essential for activating other CDKs, while CDK9 acts as a critical integrator of signals from both the cell cycle and transcriptional machinery. This review elucidates the mechanisms by which CDK7 and CDK9 regulate the mitotic process and cell cycle checkpoints, emphasizing their roles in balancing cell growth, homeostasis, and DNA repair through transcriptional control.

摘要

细胞通过正转录延伸因子b(P-TEFb,一种由CDK9、细胞周期蛋白T和转录因子组成的复合物)的转录活性来调节细胞周期相关基因的表达,包括有丝分裂所必需的细胞周期蛋白。P-TEFb与CDK7协同作用以激活RNA聚合酶。响应DNA应激,细胞周期从有丝分裂转变为修复,触发细胞周期停滞和DNA修复基因的激活。转录、细胞周期进程和DNA应激反应之间的这种紧密协调对于维持细胞完整性至关重要。细胞周期蛋白依赖性激酶CDK7和CDK9在转录和细胞周期调控中均起着核心作用。CDK7作为CDK激活激酶(CAK),对于激活其他CDK至关重要,而CDK9则作为来自细胞周期和转录机制的信号的关键整合者。本综述阐明了CDK7和CDK9调节有丝分裂过程和细胞周期检查点的机制,强调了它们通过转录控制在平衡细胞生长、体内平衡和DNA修复中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e451/12296136/cc81223417f5/KCCY_A_2485844_F0001_OC.jpg

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