通过Cdc25A Chk1介导和G2逮捕退化对dna有害的反应。
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陈小Z, Z, Gunasekera啊,Sowin TJ,罗森博格SH, Fesik年代,张H
通过Cdc25A Chk1介导和G2逮捕退化对dna有害的反应。
临床生物化学2003 278年6月13;(24):21767 - 73。Epub 2003年4月3。
- PubMed ID
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12676925 (在PubMed]
- 文摘
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紫外线和电离辐射(IR)激活DNA损伤检查点和诱导Cdc25A退化(Mailand N。Falck, J。卢卡斯,C。、Syljuasen r G。Welcker, M。Bartek, J。卢卡斯,j .科学(2000)288年,1425 - 1429;Falck, J。Mailand, N。、Syljuasen r G。Bartek, J。自然和卢卡斯j .(2001) 410年,842 - 847)。退化Cdc25A废除了咖啡因,这其中牵扯到的Chk1潜在中介(Mailand N。Falck, J。卢卡斯,C。、Syljuasen r G。Welcker, M。Bartek, J。卢卡斯,j .科学(2000)288年,1425 - 1429)。 However, the involvement of Chk1 is far from clear, because caffeine is a rather nonspecific inhibitor of the ATR/Chk1 signaling pathway. Additionally, it is not known whether DNA-damaging drugs commonly used in chemotherapy, which may activate different signal transduction pathways than UV or IR, also confer Cdc25A degradation. Herein, we show that camptothecin and doxorubicin, two widely used topoisomerase inhibitors conferring S and G2 arrest, respectively, cause the degradation of Cdc25A. Using a small interfering RNA that enables the specific elimination of Chk1 expression, we show that the observed proteolysis of Cdc25A is mediated through Chk1. Moreover, Cdc25A overexpression abrogates the Chk1-mediated degradation and overcomes the doxorubicin-induced G2 arrest through dephosphorylation and activation of Cdc2/Cdk1 in a dose-dependent manner. These results suggest that: (a) Cdc25A is involved in the G2/M transition in addition to its commonly accepted effect on G1/S progression, and (b) Chk1 mediates both S and G2 checkpoint and is thus a more ubiquitous cell cycle checkpoint mediator than previously thought.