p21 Inhibits Thr161 phosphorylation of Cdc2 to enforce the G2 DNA damage checkpoint
p21 Inhibits Thr161 phosphorylation of Cdc2 to enforce the G2 DNA damage checkpoint
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DOI：
10.1074/jbc.m005437200
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发表时间：
2000-09-29
影响因子：
4.8
通讯作者：
Medema, RH
中科院分区：
文献类型：
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作者：
Smits, VAJ;Klompmaker, R;Medema, RH
细胞周期蛋白依赖性激酶抑制剂p21是DNA损伤检查点激活后持续G（2）阻滞所需的。在这里，我们讨论了p21在G（2）中参与阻滞的机制。我们发现p21阻断了Thr（161）上Cdc2的活化磷酸化。p21不干扰Cdc2上的两个抑制性磷酸化位点Thr（14）和Tyr（15）的去磷酸化，表明p21靶向Cdc2活化中的不同事件，这与已充分描述的涉及Chk1和Cdc25C的DNA损伤检查点途径不同。综上所述，我们的数据表明，一个细胞配备了至少两个独立的途径，以确保有效抑制Cdc2的活性，在响应DNA损伤，影响积极和消极的调节磷酸化事件Cdc2。
The cyclin-dependent kinase inhibitor p21 is required for a sustained G(2) arrest after activation of the DNA damage checkpoint. Here we have addressed the mechanism by which p21 can contribute to this arrest in G(2). We show that p21 blocks the activating phosphorylation of Cdc2 on Thr(161). p21 does not interfere with the dephosphorylation of two inhibitory phosphorylation sites on Cdc2, Thr(14) and Tyr(15), indicating that p21 targets a different event in Cdc2 activation as the well described DNA damage checkpoint pathway involving Chk1 and Cdc25C. Taken together our data show that a cell is equipped with at least two independent pathways to ensure efficient inhibition of Cdc2 activity in response to DNA damage, influencing both positive and negative regulatory phosphorylation events on Cdc2.