CDK4
小结
CDK4是致癌基因，CDK4编码蛋白（cyclin-dependent kinase 4）周期蛋白依赖性激酶4是一种细胞内丝氨酸/苏氨酸激酶，其调节细胞周期G1至S期的转变。有丝分裂原刺激后，CDK4与细胞周期蛋白D（cyclin D）和细胞周期蛋白依赖性激酶6（CDK6）形成复合物，导致激酶的激活。 CDK4 / 6同时被p16INK4a（CDKN2A）负调节，其与激酶的催化结构域结合并干扰细胞周期蛋白D和ATP结合。CDK4的扩增和过表达发生在肉瘤，胶质母细胞瘤和乳腺癌中。CDK4 / 6抑制剂已在某些实体瘤中显示出临床功效，包括乳腺癌和非小细胞肺癌。
CDK4 (cyclin-dependent kinase 4) is a serine/threonine kinase that regulates the cell cycle G1 to S phase transition. Upon mitogen stimulation, CDK4 forms a complex with cyclin D and cyclin-dependent kinase 6 (CDK6), which leads to activation of the kinases. The active CDK4/CDK6 complex then phosphorylates and inactivates retinoblastoma (RB), thereby inducing the gene expression program regulated by the E2F family of transcription factors, which is important in cell cycle progression. CDK4/6 are in turn negatively regulated by p16INK4a (CDKN2A), which binds to the catalytic domains of the kinases and interferes with cyclin D and ATP binding. Amplification and overexpression of CDK4 occur in sarcomas, glioblastoma and breast cancers. CDK4/6 inhibitors have shown clinical efficacy in certain solid tumors, including breast and non-small cell lung cancer. Furthermore, CDK4/6 inhibition can trigger anti-tumor immunity by promoting cytotoxic T-cell-mediated clearance of tumor cells.