C. elegans CAND-1 regulates cullin neddylation, cell proliferation and morphogenesis in specific tissues.
C. elegans CAND-1 regulates cullin neddylation, cell proliferation and morphogenesis in specific tissues.
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DOI：
10.1016/j.ydbio.2010.07.020
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发表时间：
2010-10-01
影响因子：
2.7
通讯作者：
Kipreos ET
中科院分区：
文献类型：
--
作者：
Bosu DR;Feng H;Min K;Kim Y;Wallenfang MR;Kipreos ET
Cullin-RING泛素连接酶（CRLs）是真核生物多种发育和细胞过程的重要调节因子。CAND1是一种CRL的生化抑制剂，但在植物和哺乳动物细胞中已被证明可以促进CRL的活性。在这里，我们分析了CAND1在发展中的后生动物有机体中的功能。秀丽隐杆线虫的CAND-1能够与所有cullins结合，并且我们表明它在体内与CUL-2和CUL-4物理相互作用。泛素样蛋白Nedd8的共价附着是动植物扑杀活性所必需的。在cand-1突变体中，CUL-2和CUL-4的类木化异构体水平升高，表明cand-1是cullin类木化的负调节因子。cand-1突变体对cullin活性的部分丧失非常敏感，这表明cand-1促进了CRL功能。rand -1突变体表现出不渗透的表型，包括发育停滞，外阴和尾巴的形态缺陷，以及生殖力降低。and-1突变体与cul-1和lin-23突变体具有多缝细胞分裂、缺陷叶片形成和谷氨酸受体GLR-1靶点SCFLIN-23积累的表型。观察到，cand-1突变体具有与SCFLIN-23复合物缺失相关的表型，但缺乏与其他特定CRL复合物相关的表型，这表明cand-1对于不同CRL复合物的活性是不同的。
Cullin-RING ubiquitin ligases (CRLs) are critical regulators of multiple developmental and cellular processes in eukaryotes. CAND1 is a biochemical inhibitor of CRLs, yet has been shown to promote CRL activity in plant and mammalian cells. Here we analyze CAND1 function in the context of a developing metazoan organism. C. elegans CAND-1 is capable of binding to all of the cullins, and we show that it physically interacts with CUL-2 and CUL-4 in vivo. The covalent attachment of the ubiquitin-like protein Nedd8 is required for cullin activity in animals and plants. In cand-1 mutants, the levels of the neddylated isoforms of CUL-2 and CUL-4 are increased, indicating that CAND-1 is a negative regulator of cullin neddylation. cand-1 mutants are hypersensitive to the partial loss of cullin activity, suggesting that CAND-1 facilitates CRL functions. cand-1 mutants exhibit impenetrant phenotypes, including developmental arrest, morphological defects of the vulva and tail, and reduced fecundity. cand-1 mutants share with cul-1 and lin-23 mutants the phenotypes of supernumerary seam cell divisions, defective alae formation, and the accumulation of the SCFLIN-23 target the glutamate receptor GLR-1. The observation that cand-1 mutants have phenotypes associated with the loss of the SCFLIN-23 complex, but lack phenotypes associated with other specific CRL complexes, suggests that CAND-1 is differentially required for the activity of distinct CRL complexes.
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影响因子：
--
作者：
Cope GA;Deshaies RJ
通讯作者：
Deshaies RJ
影响因子：
64.5
作者：
Duda, David M.;Borg, Laura A.;Scott, Daniel C.;Hunt, Harold W.;Hammel, Michal;Schulman, Brenda A.
通讯作者：
Schulman, Brenda A.
DOI：
10.1006/bbrc.2000.2260
发表时间：
2000-03-05
影响因子：
3.1
作者：
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通讯作者：
Mitani, S
影响因子：
7.4
作者：
Cheng, YF;Dai, XH;Zhao, Y
通讯作者：
Zhao, Y
影响因子：
64.5
作者：
CIECHANOVER, A;FINLEY, D;VARSHAVSKY, A
通讯作者：
VARSHAVSKY, A