Role of individual subunits of the Neurospora crassa CSN complex in regulation of deneddylation and stability of cullin proteins.
Role of individual subunits of the Neurospora crassa CSN complex in regulation of deneddylation and stability of cullin proteins.
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粗糙脉孢菌 CSN 复合体的各个亚基在调节 Cullin 蛋白的 Deneddylation 和稳定性中的作用
DOI：
10.1371/journal.pgen.1001232
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发表时间：
2010-12-02
期刊：
影响因子：
4.5
通讯作者：
He Q
中科院分区：
文献类型：
--
作者：
Wang J;Hu Q;Chen H;Zhou Z;Li W;Wang Y;Li S;He Q
Cop 9信号体（CSN）是一种进化上保守的多功能复合物，在真核生物中控制泛素依赖的蛋白质降解。我们发现七个CSN亚基在粗糙脉孢菌在以前的研究中，但只有一个亚基，CSN-2，功能的特点。在这项研究中，我们建立了敲除突变体的其余个别CSN亚基在N。粗鲁。通过表型观察，我们发现CSN-1、CSN-2、CSN-4、CSN-5、CSN-6或CSN-7的缺失导致生长、分生孢子和昼夜节律的严重缺陷;缺陷的严重程度是基因依赖的。出乎意料的是，CSN-3敲除突变体显示出与野生型N.粗鲁。与这些表型观察结果一致，csn-1，csn-2，csn-4，csn-5，csn-6或csn-7突变体中cullin蛋白的去eddylation显著受损，而csn-3的缺失不会导致cullin蛋白的去eddylation/去eddylation状态的任何改变。我们进一步证明，CSN-1，CSN-2，CSN-4，CSN-5，CSN-6和CSN-7，而不是CSN-3，是维持SCF复合物中Cul 1和Cul 3-BTB E3中Cul 3和BTB蛋白的稳定性所必需的，而五个CSN亚基，而不是CSN-3和CSN-5，也是维持SCF复合物中SKP-1稳定性所必需的。所有7个CSN亚基都是维持Cul 4-DDB 1复合物稳定性所必需的。此外，CSN-3也是维持SCFFWD-1复合物中CSN-2亚基和FWD-1稳定性所必需的。总之，这些结果不仅提供了功能的洞察到CSN复合物中的各个亚基的不同作用，但也建立了一个功能框架，了解在生物过程中的CSN复合物的多种功能。
The Cop9 signalosome (CSN) is an evolutionarily conserved multifunctional complex that controls ubiquitin-dependent protein degradation in eukaryotes. We found seven CSN subunits in Neurospora crassa in a previous study, but only one subunit, CSN-2, was functionally characterized. In this study, we created knockout mutants for the remaining individual CSN subunits in N. crassa. By phenotypic observation, we found that loss of CSN-1, CSN-2, CSN-4, CSN-5, CSN-6, or CSN-7 resulted in severe defects in growth, conidiation, and circadian rhythm; the defect severity was gene-dependent. Unexpectedly, CSN-3 knockout mutants displayed the same phenotype as wild-type N. crassa. Consistent with these phenotypic observations, deneddylation of cullin proteins in csn-1, csn-2, csn-4, csn-5, csn-6, or csn-7 mutants was dramatically impaired, while deletion of csn-3 did not cause any alteration in the neddylation/deneddylation state of cullins. We further demonstrated that CSN-1, CSN-2, CSN-4, CSN-5, CSN-6, and CSN-7, but not CSN-3, were essential for maintaining the stability of Cul1 in SCF complexes and Cul3 and BTB proteins in Cul3-BTB E3s, while five of the CSN subunits, but not CSN-3 and CSN-5, were also required for maintaining the stability of SKP-1 in SCF complexes. All seven CSN subunits were necessary for maintaining the stability of Cul4-DDB1 complexes. In addition, CSN-3 was also required for maintaining the stability of the CSN-2 subunit and FWD-1 in the SCFFWD-1 complex. Together, these results not only provide functional insights into the different roles of individual subunits in the CSN complex, but also establish a functional framework for understanding the multiple functions of the CSN complex in biological processes.
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影响因子：
--
作者：
Cope GA;Deshaies RJ
通讯作者：
Deshaies RJ
影响因子：
2.3
作者：
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影响因子：
5.3
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作者：
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通讯作者：
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影响因子：
3.6
作者：
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通讯作者：
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