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有读书笔记有附件The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis

2 阿平 添加于 2009-12-11 05:27 | 2671 次阅读 | 0 个评论
  •  作 者

    Maerki S, Olma MH, Staubli T, Steigemann P, Gerlich DW, Quadroni M, Sumara I, Peter M
  •  摘 要

    Cul3 (Cullin3)-based E3 ubiquitin ligases recently emerged as critical regulators of mitosis. In this study, we identify two mammalian BTB (Bric-a-brac–Tramtrack–Broad complex)-Kelch proteins, KLHL21 and KLHL22, that interact with Cul3 and are required for efficient chromosome alignment. Interestingly, KLHL21 but not KLHL22 is necessary for cytokinesis and regulates translocation of the chromosomal passenger complex (CPC) from chromosomes to the spindle midzone in anaphase, similar to the previously described BTB-Kelch proteins KLHL9 and KLHL13. KLHL21 directly binds to Aurora B and mediates ubiquitination of Aurora B in vitro. In contrast to KLHL9 and KLHL13, KLHL21 localizes to midzone microtubules in anaphase and recruits Aurora B and Cul3 to this region. Together, our results suggest that different Cul3 adaptors nonredundantly regulate Aurora B during mitosis, possibly by ubiquitinating different pools of Aurora B at distinct subcellular localizations.
  •  详细资料

    • 文献种类: Journal Article
    • 期刊名称: The Journal of Cell Biology
    • 期刊缩写: The Journal of Cell Biology
    • ISBN: 0021-9525
  • 学科领域 生物医药 » 生物学

  •  标 签

    Aurora 
  • 相关链接 DOI URL 

  •  附 件

    PDF附件The Cul3-KLHL21 E3 ubiquitin ligase targets Aurora B to midzone microtubules in anaphase and is required for cytokinesis 
  •  阿平 的文献笔记  订阅

    谁抓住了有丝分裂的过客

    chromosomal passanger complex(CPC)是有丝分裂中的重要角色,在metaphase时,他们位于kinetochore,anaphase之后,又转移到midzone spindle那里,所以才有passenger一说。但是这种位置改变都只是在显微镜下观察到的,实际上发生的是什么,那还很难说,而且更多证据认为CPC先在kinetochore被降解,然后其他的CPC又浓聚到midzone spindle那里,所以很可能是狸猫换太子,而不是passenger。

    这篇文章找到了BTB proteins中的KLHL21和KLHL22两个蛋白都与有丝分裂相关。其中KLHL21与CPC在metaphase到anaphase的过渡中出现未知转移相关。siRNA KLHL21之后,CPC会滞留在chromosome上,而midzone那里的信号很弱,进而导致cytokinesis失败。说明KLHL21的功能是帮助CPC转移的过程,此功能与泛素连接酶Cul3被siRNA后的现象相似。加之CPC,KLHL21和Cul3可形成复合物,Aurora B被Cul3连接酶搞到泛素化,从而从chromosome上面离开。那么Aurora B被泛素化后并离开chromosome后去哪里了,一是可能被彻底泛素化消失了,另一个则是可能带着泛素化的伤疤被转移到midzone spindle了。我觉得文章给出的KLHL21能定位到midzone spindle MT并募集更多的Aurora B到midzone那里,就支持后面的假设。

     

    KLHL22有点奇怪,siRNA后细胞要么停滞在prometaphase,要么就死翘翘了。估计也是有spindle checkpoint方面的影响,看看图片,prometaphase的纺锤体一开始形成了,但染色体没有成功联会,最终纺锤体聚合也出现了问题,总之细胞就呆在prometaphase没出去,在我看来这是挺重要的现象,值得关注。

     

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