SAS-6定义了秀丽隐杆线虫和人类细胞中中心体复制所需的一个蛋白质家族。

SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells.

作者信息

Leidel Sebastian, Delattre Marie, Cerutti Lorenzo, Baumer Karine, Gönczy Pierre

机构信息

Swiss Institute for Experimental Cancer Research (ISREC), CH-1066 Epalinges/Lausanne, Switzerland.

出版信息

Nat Cell Biol. 2005 Feb;7(2):115-25. doi: 10.1038/ncb1220.

Abstract

The mechanisms that ensure centrosome duplication are poorly understood. In Caenorhabditis elegans, ZYG-1, SAS-4, SAS-5 and SPD-2 are required for centriole formation. However, it is unclear whether these proteins have functional homologues in other organisms. Here, we identify SAS-6 as a component that is required for daughter centriole formation in C. elegans. SAS-6 is a coiled-coil protein that is recruited to centrioles at the onset of the centrosome duplication cycle. Our analysis indicates that SAS-6 and SAS-5 associate and that this interaction, as well as ZYG-1 function, is required for SAS-6 centriolar recruitment. SAS-6 is the founding member of an evolutionarily conserved protein family that contains the novel PISA motif. We investigated the function of the human homologue of SAS-6. GFP-HsSAS-6 localizes to centrosomes and its overexpression results in excess foci-bearing centriolar markers. Furthermore, siRNA-mediated inactivation of HsSAS-6 in U2OS cells abrogates centrosome overduplication following aphidicolin treatment and interferes with the normal centrosome duplication cycle. Therefore, HsSAS-6 is also required for centrosome duplication, indicating that the function of SAS-6-related proteins has been widely conserved during evolution.

摘要

确保中心体复制的机制目前仍知之甚少。在秀丽隐杆线虫中,ZYG-1、SAS-4、SAS-5和SPD-2是中心粒形成所必需的。然而,尚不清楚这些蛋白质在其他生物中是否具有功能同源物。在此,我们鉴定出SAS-6是秀丽隐杆线虫中形成子代中心粒所必需的一个成分。SAS-6是一种卷曲螺旋蛋白,在中心体复制周期开始时被招募到中心粒。我们的分析表明,SAS-6与SAS-5相互作用,并且这种相互作用以及ZYG-1的功能对于SAS-6在中心粒上的招募是必需的。SAS-6是一个进化上保守的蛋白质家族的创始成员,该家族包含新的PISA基序。我们研究了SAS-6的人类同源物的功能。GFP-HsSAS-6定位于中心体,其过表达导致带有中心粒标记的焦点增多。此外,在U2OS细胞中,通过siRNA介导使HsSAS-6失活,可消除阿非科林处理后的中心体过度复制,并干扰正常的中心体复制周期。因此,HsSAS-6也是中心体复制所必需的,这表明SAS-6相关蛋白的功能在进化过程中已被广泛保守。

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