CDK12
小结
CDK12是抑癌基因，CDK12编码蛋白（Cyclin-dependent kinase 12）为细胞周期蛋白依赖性激酶12，是一种细胞内激酶参与细胞周期调控和调节许多DNA损伤应答基因转录延伸的激酶。CDK12与RNA聚合酶II（RNAP）的C-末端结构域（CTD）相互作用并磷酸化，并与Cyclin K复合，通过调节DNA损伤应答基因（如BRCA1、ATR、FANCI和FANCd2）的表达来维持基因组稳定性。CDK12/细胞周期蛋白K复合物的缺失使HEK293细胞对喜树碱、依托泊苷和丝裂霉素C等多种DNA损伤剂敏感。CDK12是卵巢癌最常见的体细胞突变基因之一，与维持基因组稳定性有关。
CDK12 (Cyclin-dependent kinase 12) is a kinase involved in the regulation of the cell cycle and the regulation of transcriptional elongation of many DNA-damage-response genes. CDK12 interacts with and phosphorylates the C-terminal domain (CTD) of RNA polymerase II (RNAP) in vitro and complexes with Cyclin K to maintain genomic stability via regulation of the expression of DNA damage response genes, such as BRCA1, ATR, FANCI and FANCD2. Loss of the CDK12/cyclin K complex renders HEK293 cells sensitive to various DNA damaging agents, including camptothecin, etoposide and mitomycin C. CDK12 is one of the most frequently somatically mutated genes in ovarian cancer, which is consistent with its role in the maintenance of genomic stability. However, amplification of CDK12 is seen in breast cancer and has been associated with tumor invasiveness, transcriptional addiction and PARP-inhibitor resistance, suggesting that CDK12 may be an oncogene in some contexts.