Neurospora COP9 signalosome integrity plays major roles for hyphal growth, conidial development, and circadian function.
Neurospora COP9 signalosome integrity plays major roles for hyphal growth, conidial development, and circadian function.
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脉孢菌 COP9 信号体完整性在菌丝生长、分生孢子发育和昼夜节律功能中发挥着重要作用
DOI：
10.1371/journal.pgen.1002712
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发表时间：
2012
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：
Zhou Z;Wang Y;Cai G;He Q
COP9信号体（CSN）是一种高度保守的多功能复合体，具有两个主要的生化作用：从cullin蛋白上切割NEDD8和维持CRL组分的稳定性。我们利用突变分析证实，CSN-5亚基的JAMM结构域负责从粗神经孢子虫cullin蛋白中切割NEDD8。CSN-5 JAMM结构域金属结合基元（EXn hxhx10d）关键残基的点突变破坏了CSN的去基化活性，但不干扰CSN复合物的组装或CSN与cullin蛋白之间的相互作用。令人惊讶的是，具有突变JAMM结构域的CSN-5部分挽救了在CSN-5突变体中观察到的表型缺陷。我们发现，即使没有去eddyylation活性，CSN也能在体内部分维持SCFFWD-1复合物的稳定性，部分恢复生物钟蛋白FREQUENCY （FRQ）的降解。此外，我们发现含有突变体CSN-5的CSN有效地阻止了crl底物受体的降解。最后，我们发现，缺失CAND1同源基因对白杨孢子的昼夜节律影响不大。我们的研究结果表明，CSN的完整性在棘草菌丝生长、分生孢子发育和昼夜节律功能中起着重要作用。
The COP9 signalosome (CSN) is a highly conserved multifunctional complex that has two major biochemical roles: cleaving NEDD8 from cullin proteins and maintaining the stability of CRL components. We used mutation analysis to confirm that the JAMM domain of the CSN-5 subunit is responsible for NEDD8 cleavage from cullin proteins in Neurospora crassa. Point mutations of key residues in the metal-binding motif (EXn HXHX10 D) of the CSN-5 JAMM domain disrupted CSN deneddylation activity without interfering with assembly of the CSN complex or interactions between CSN and cullin proteins. Surprisingly, CSN-5 with a mutated JAMM domain partially rescued the phenotypic defects observed in a csn-5 mutant. We found that, even without its deneddylation activity, the CSN can partially maintain the stability of the SCFFWD-1 complex and partially restore the degradation of the circadian clock protein FREQUENCY (FRQ) in vivo. Furthermore, we showed that CSN containing mutant CSN-5 efficiently prevents degradation of the substrate receptors of CRLs. Finally, we found that deletion of the CAND1 ortholog in N. crassa had little effect on the conidiation circadian rhythm. Our results suggest that CSN integrity plays major roles in hyphal growth, conidial development, and circadian function in N. crassa.
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影响因子：
--
作者：
Cope GA;Deshaies RJ
通讯作者：
Deshaies RJ
影响因子：
9.8
作者：
Ambroggio XI;Rees DC;Deshaies RJ
通讯作者：
Deshaies RJ
影响因子：
5.3
作者：
Luke-Glaser, Sarah;Roy, Marcia;Pintard, Lionel
通讯作者：
Pintard, Lionel
影响因子：
3.6
作者：
Busch, S;Eckert, SE;Braus, GH
通讯作者：
Braus, GH
影响因子：
10.5
作者：
He, Q;Cheng, P;Liu, Y
通讯作者：
Liu, Y