The Giardia cell cycle progresses independently of the anaphase-promoting complex
The Giardia cell cycle progresses independently of the anaphase-promoting complex
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DOI：
10.1242/jcs.121632
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发表时间：
2013-05-15
影响因子：
4
通讯作者：
Cande, W. Zacheus
中科院分区：
文献类型：
--
作者：
Gourguechon, Stephane;Holt, Liam J.;Cande, W. Zacheus
大多数细胞周期调控研究都是在代表真核生物领域很小一部分的模型生物中进行的。高度分化的人类病原体肠贾第鞭毛虫是研究真核生物途径保护的理想选择。尽管贾第鞭毛虫有许多细胞周期调节成分，但其基因组缺乏所有后期促进复合体(APC)成分。在目前的研究中，我们发现贾第鞭毛虫中的一个有丝分裂周期蛋白对于进入有丝分裂是必不可少的。值得注意的是，贾第鞭毛虫周期蛋白B缺乏由APC和泛素结合介导的及时降解所需的保守的N末端基序。贾第鞭毛虫周期蛋白B在分裂酵母中的表达是有毒的，导致早期停滞，这种毒性可以通过添加分裂酵母降解基序来抑制。在贾第虫细胞有丝分裂过程中，细胞周期蛋白B被降解，但这种降解似乎不依赖于泛素化途径。其他假定的APC底物，极光和类似Polo的激酶，也没有显示泛素化的证据。这是第一个不受APC调控的有丝分裂的例子，可能反映了一种进化的古老的细胞周期调控形式。
Most cell cycle regulation research has been conducted in model organisms representing a very small part of the eukaryotic domain. The highly divergent human pathogen Giardia intestinalis is ideal for studying the conservation of eukaryotic pathways. Although Giardia has many cell cycle regulatory components, its genome lacks all anaphase-promoting complex (APC) components. In the present study, we show that a single mitotic cyclin in Giardia is essential for progression into mitosis. Strikingly, Giardia cyclin B lacks the conserved N-terminal motif required for timely degradation mediated by the APC and ubiquitin conjugation. Expression of Giardia cyclin B in fission yeast is toxic, leading to a prophase arrest, and this toxicity is suppressed by the addition of a fission yeast degradation motif. Cyclin B is degraded during mitosis in Giardia cells, but this degradation appears to be independent of the ubiquitination pathway. Other putative APC substrates, aurora and polo-like kinases, also show no evidence of ubiquitination. This is the first example of mitosis not regulated by the APC and might reflect an evolutionary ancient form of cell cycle regulation.