Apc8的C端无序循环域解锁了APC/C线性激活
Sarah Darling1, Kazuyuki Fujimitsu1, Kim Hou Chia1
1Cell Cycle Control Group, University College London (UCL) Cancer Institute, London WC1E 6DD, UK.
亚纳酶促进复合体/循环体 (APC/C) 使用新发现的循环 (Apc8-L) 来招募蛋白质,在细胞分裂过程中激活它. 这一发现揭示了对调节APC/C的新见解,APC/C是细胞周期的关键因素.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 亚纳酶促进复合体/循环体 (APC/C) 是一个关键的E3酶,调节细胞循环.
- APC/C活动是由一个涉及Apc1-300L循环的自身抑制机制控制的.
- Apc1-300L的酸化缓解了自身抑制,但其他调节环仍然在很大程度上没有特征.
研究的目的:
- 调查APC/C调节中未被探索的无序循环的作用.
- 为了阐明APC/C在线索分裂过程中被激活的机制.
主要方法:
- 循环缺陷的APC/C突变体的系统分析.
- 生物化学试验用于研究蛋白质-蛋白质相互作用和复杂的形成.
主要成果:
- Apc8的C端环 (Apc8-L) 对于线性APC/C激活至关重要.
- Apc8-L招募了CDK适配蛋白Xe-p9 / Cks2.2. 这种蛋白质.
- 通过Apc8-L招募Xe-p9-CDK-CycB复合物,促进Apc1-300L的酸化和去除,从而导致活性APC/CCdc20.
- 无论是Apc8-L还是Apc3-L的损失都会导致APC/C.的完全线粒性失活.
结论:
- Apc8-L通过促进激酶的招募,在APC/C激活中发挥着关键作用.
- 这项研究揭示了涉及多个APC/C循环调节其活动的协同机制.
- 这些发现扩大了对宏分子复合体调节和细胞周期控制的理解.
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