Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis.
Chk2/Cds1 protein kinase blocks apoptosis during early development of Xenopus laevis.
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Chk2/Cds1 蛋白激酶可阻断非洲爪蟾早期发育过程中的细胞凋亡。
DOI：
10.1002/dvdy.20449
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发表时间：
2005
期刊：
影响因子：
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通讯作者：
Sible,JillC
中科院分区：
文献类型：
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作者：
Wroble,BrianN;Sible,JillC
非洲爪哇早期胚胎具有细胞周期，不会在检查站对受损的DNA做出反应。在中期胚泡过渡(MBT)时，DNA受损的胚胎会发生细胞凋亡。在MBT之后，DNA损伤会触发细胞周期停滞，而不是细胞凋亡。从检查点非调控周期到检查点调控周期的转变使得Xenopus胚胎迫切需要研究基因组损伤的调控机制。DNA损伤检查点是由Chk2/CDs1激酶介导的。相互矛盾的证据表明Chk2是细胞凋亡的抑制者或促进者。为了更好地了解Chk2的发育功能，我们在非洲爪哇胚胎中表达了野生型(Wt)和显性阴性(DN)Chk2。WT-Chk2由于CDc25A的降解和细胞周期蛋白依赖性激酶的磷酸化而创建了一个MBT前检查点。表达dN-Chk2的胚胎发育正常，直到原肠形成，然后发生细胞凋亡。相反，低剂量的wt-Chk2可阻断辐射诱导的细胞凋亡。因此，Chk2在细胞周期停滞或细胞凋亡之间进行切换，以响应基因组攻击。发展动力学233：1359-1365,2005。©2005 Wiley-Liss Inc.
EarlyXenopus laevisembryos possess cell cycles that do not arrest at checkpoints in response to damaged DNA. At the midblastula transition (MBT), embryos with damaged DNA undergo apoptosis. After the MBT, DNA damage triggers cell cycle arrest rather than apoptosis. The transition from checkpoint‐unregulated to checkpoint‐regulated cycles makesXenopusembryos compelling for studying mechanisms regulating response to genomic damage. The DNA damage checkpoint is mediated by the Chk2/Cds1 kinase. Conflicting evidence implicates Chk2 as an inhibitor or promoter of apoptosis. To better understand the developmental function of Chk2, we expressed wild‐type (wt) and dominant‐negative (DN) Chk2 inXenopusembryos. Wt‐Chk2 created a pre‐MBT checkpoint due to degradation of Cdc25A and phosphorylation of cyclin‐dependent kinases. Embryos expressing DN‐Chk2 developed normally until gastrulation and then underwent apoptosis. Conversely, low doses of wt‐Chk2 blocked radiation‐induced apoptosis. Therefore, Chk2 operates at a switch between cell cycle arrest or apoptosis in response to genomic assaults. Developmental Dynamics 233:1359–1365, 2005. © 2005 Wiley‐Liss, Inc.