Functionally Distinct Isoforms of Cik1 Are Differentially Regulated by APC/C-Mediated Proteolysis
Functionally Distinct Isoforms of Cik1 Are Differentially Regulated by APC/C-Mediated Proteolysis
复制标题
DOI：
10.1016/j.molcel.2009.01.032
复制
发表时间：
2009-03-13
期刊：
影响因子：
16
通讯作者：
Toczyski, David P.
中科院分区：
文献类型：
--
作者：
Benanti, Jennifer A.;Matyskiela, Mary E.;Toczyski, David P.
在交配过程中，Cik1和kinesin Kar3共同控制着有丝分裂纺锤体和核融合。在这里，我们证明了有两种Cik1亚型，有丝分裂形式包括后期促进复合体/环体(APC/C)泛素化所需的N-末端结构域。在营养生长期间，Cik1在有丝分裂期间表达，并调节有丝分裂纺锤体，允许准确的染色体分离。有丝分裂后，APC/C(CDH1)以Cik1为靶标进行泛素介导的蛋白分解。当接触交配信息素α因子时，一个较小的抗APC/C的Cik1亚型从另一个转录起点表达。这种较短的Cik1亚型是稳定的，不能被APC/C(CDH1)泛素化。此外，这两种Cik1亚型在功能上是不同的。只表达长亚型的细胞有核融合缺陷，而只表达短亚型的细胞染色体损失率增加。这些结果表明转录调控和APC/C介导的蛋白分解是耦合的。
Cik1, in association with the kinesin Kar3, controls both the mitotic spindle and nuclear fusion during mating. Here, we show that there are two Cik1 isoforms, and that the mitotic form includes an N-terminal domain required for ubiquitination by the Anaphase-Promoting Complex/Cyclosome (APC/C). During vegetative growth, Cik1 is expressed during mitosis and regulates the mitotic spindle, allowing for accurate chromosome segregation. After mitosis, APC/C(Cdh1) targets Cik1 for ubiquitin-mediated proteolysis. Upon exposure to the mating pheromone alpha factor, a smaller APC/C-resistant Cik1 isoform is expressed from an alternate transcriptional start site. This shorter Cik1 isoform is stable and cannot be ubiquitinated by APC/C(Cdh1). Moreover, the two Cik1 isoforms are functionally distinct. Cells that express only the long isoform have defects in nuclear fusion, whereas cells expressing only the short isoform have an increased rate of chromosome loss. These results demonstrate a coupling of transcriptional regulation and APC/C-mediated proteolysis.