Choosing anticancer drug targets in the postgenomic era
Choosing anticancer drug targets in the postgenomic era
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DOI：
10.1172/jci8888
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发表时间：
1999-12-01
影响因子：
15.9
通讯作者：
Kaelin, WG
中科院分区：
文献类型：
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作者：
Kaelin, WG
PRb和p53通路的简化视图。CDK4和CDK6受G1期细胞周期蛋白(如D型细胞周期蛋白)正向调节，受CDK抑制剂(如p16/INK4A)负向调节。CDK4和CDK6磷酸化，从而抑制视网膜母细胞瘤蛋白(PRB)。PRb与E2F转录因子家族成员形成复合体。这些复合体抑制E2F反应启动子的转录。P53是一种序列特异性DNA结合蛋白，可转录激活p21/WAF1和Bax等靶基因。HDM2沉默P53转录激活域，并针对P53进行降解。ARF拮抗Hdm2。如虚线所示，这些看起来是线性的通路受到串扰的影响，这将它们连接到一个更复杂的监管网络中。
Simplified views of the pRB and p53 pathways. The cdk4 and cdk6 kinases are positively regulated by G1 cyclins such as the D-type cyclins and negatively regulated by cdk inhibitors such as p16/INK4A. Cdk4 and Cdk6 phosphorylate, and thus inhibit, the retinoblastoma protein (pRB). pRB forms complexes with members of the E2F transcription factor family. These complexes repress transcription from E2F-responsive promoters. p53 is a sequence-specific DNA-binding protein that transcriptionally activates target genes such as p21/WAF1 and BAX. HDM2 silences the p53 transcriptional activation domain and targets p53 for degradation. ARF antagonizes HDM2. As indicated by the dashed lines, these apparently linear pathways are subject to cross-talk, which links them into a more complex regulatory network.