Bregman D B, Pestell R G, Kidd V J
Dept. of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Front Biosci. 2000 Feb 1;5:D244-57. doi: 10.2741/bregman.
The cell cycle and transcription by RNA polymerase II (RNAP II) are closely related. They utilize shared components. RNAP II transcriptional activity is modulated during the cell cycle. Cell cycle dependent changes in the phosphorylation status of the carboxyl-terminal domain (CTD) of the largest subunit of RNAP II (RNAP II-LS) alter transcription. Several CTD kinases are members of the cyclin-dependent kinase (cdk) superfamily, including p34cdc2 (cdk1), cdk7, cdk8, and cdk9. Each of these cdks, with their respective cyclin partners, have been linked to cell cycle regulatory events. Other CTD kinases such as casein kinase II (CKII) and c-abl have also been implicated in cell cycle dependent modifications of the CTD. In addition, the stalling of RNAP II complexes at DNA lesions helps stimulate p53 accumulation which largely determines the cell's DNA damage response, including cell cycle arrest. Alzheimer's disease pathology results partially from activation of mitotic cdks in postmitotic neurons which can phosphorylate RNAP II-LS and other targets.
细胞周期与RNA聚合酶II（RNAP II）转录密切相关。它们利用共享组件。RNAP II转录活性在细胞周期中受到调节。细胞周期依赖性的RNAP II最大亚基（RNAP II-LS）羧基末端结构域（CTD）磷酸化状态的变化会改变转录。几种CTD激酶是细胞周期蛋白依赖性激酶（cdk）超家族的成员，包括p34cdc2（cdk1）、cdk7、cdk8和cdk9。这些cdk中的每一种与其各自的细胞周期蛋白伴侣都与细胞周期调节事件有关。其他CTD激酶，如酪蛋白激酶II（CKII）和c-abl，也与CTD的细胞周期依赖性修饰有关。此外，RNAP II复合物在DNA损伤处的停滞有助于刺激p53积累，这在很大程度上决定了细胞的DNA损伤反应，包括细胞周期停滞。阿尔茨海默病病理学部分源于有丝分裂cdk在有丝分裂后神经元中的激活，这些cdk可使RNAP II-LS和其他靶点磷酸化。
