Cln3通过SBF结合抑制剂Whi5的酸化来激活G1特异性转录
Robertus A M de Bruin1, W Hayes McDonald, Tatyana I Kalashnikova
1Department of Molecular Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Cell
|June 24, 2004
概括
Whi5 作为发芽酵母中的 G1 特定的转录抑制剂,控制细胞循环启动. 它的无活化绕过了Cln3/CDK的要求,揭示了它在细胞循环调节中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 发芽的酵母细胞周期由G1特异的转录激活启动,由Cln3/cyclin-dependent kinase (CDK) 驱动.
- 识别Cln3/CDK的直接点对于理解细胞循环控制机制至关重要.
研究的目的:
- 确定参与细胞循环启动的Cln3/CDK的新目标.
- 在G1特定基因调节和细胞周期进展的背景下阐明Whi5的功能.
主要方法:
- 多维蛋白相互作用技术 (MudPIT) 用于分析SBF和MBF转录因子复合体.
- 进行了涉及Whi5无活化和过度表达的功能测试.
- 对Whi5与G1特异性促进体的关联以及Cln3/CDK对Whi5解离的影响的分析.
主要成果:
- Whi5被确定为SBF转录因子复合物的组成部分,但不是MBF.
- Whi5 失活导致过早的 G1 基因表达和芽,绕过 Cln3.3 的需要.
- 在转录激活时,Whi5与G1促进体分离,这一过程是由Cln3/CDK酸化促进的.
结论:
- Whi5作为一种G1特异性的转录抑制剂,类似于哺乳动物Rb.
- Cln3/CDK通过酸化对抗Whi5活性,促进其解离,并使细胞循环启动.
- Whi5是发芽酵母G1到S阶段过渡的关键调节者.
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