一种依赖于环素的激酶抑制剂,Dacapo,是Drosophila胚胎生成期间及时退出细胞循环的必要条件
J C de Nooij1, M A Letendre, I K Hariharan
1Massachusetts General Hospital Cancer Center, Charlestown 02129, USA.
Cell
|December 27, 1996
概括
达卡波 (dap) 是一种新型cdk抑制剂,通过调节细胞周期的退出,对胚胎发育至关重要. 过度表达会破坏细胞循环,而突变会延迟这种退出,影响细胞静止.
科学领域:
- 发展生物学 发展生物学
- 细胞循环规则 细胞循环规则
- 分子遗传学 分子遗传学
背景情况:
- 拉普1 GTPase 途径参与各种细胞过程.
- 循环素依赖性激酶 (cdk) 抑制剂调节细胞循环的进展.
- 哺乳动物cdk抑制剂具有多种作用,但它们在发育中的重要性尚未完全理解.
研究的目的:
- 为了识别与Rap1 GTPase相互作用的基因.
- 为了描述一种新鲜的多索菲拉基因的功能, dacapo (dap).
- 阐明DAP在胚胎发育和细胞周期控制中的作用.
主要方法:
- 在Drosophila中进行基因查,以确定相互作用的基因.
- 在体外测试以评估dacapo对cyclin-cdk.dk的抑制活性.
- 在Drosophila眼睛发育中的过度表达研究.
- 基因相互作用研究与视网膜母细胞瘤同源 (Rbf) 和cyclin E.
- 在胚胎发生过程中分析DAP表达模式.
- 在DAP突变胚胎中检查细胞周期进展和静止状态.
主要成果:
- 确定了达卡波 (dap) 作为与Rap1 GTPase相互作用的Drosophila基因.
- 达卡波属于p21/p27家族的cdk抑制剂.
- 对于正常的Drosophila胚胎发育,Dap是必不可少的.
- 达卡波在体外抑制了环林-cdk的活性.
- 在眼睛发育过程中过度表达DAP会破坏细胞循环的进展,并与Rbf和环林E发生遗传相互作用.
- 达普表达与胚胎发生期间的细胞周期退出相关.
- 达普突变胚胎表现出细胞周期退出延迟,导致额外的细胞周期和随后的静止.
结论:
- 达卡波是Drosophila胚胎发生过程中细胞周期退出的关键调节者.
- 它的功能对于实现精确定时的细胞周期退出至关重要.
- 达卡波代表了一个关键的发育控制点,与以前研究的哺乳动物cdk抑制剂不同.
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