Systematic analysis of the physiological importance of deubiquitinating enzymes.
Systematic analysis of the physiological importance of deubiquitinating enzymes.
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DOI：
10.1371/journal.pone.0043112
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Todi SV
中科院分区：
文献类型：
--
作者：
Tsou WL;Sheedlo MJ;Morrow ME;Blount JR;McGregor KM;Das C;Todi SV
去泛素化酶（DUBs）是通过泛素控制蛋白质的翻译后修饰并进而调节多种细胞途径的蛋白酶。尽管在结构和分子水平上对DUB生物学的了解越来越多，但对大多数DUB的生理重要性知之甚少。在这里，我们系统地确定DUBs编码的果蝇基因组，并检查其在体内的生理重要性。通过结构域分析，我们发现了41个果蝇DUB，其中大部分具有人类直系同源物。系统性地敲除果蝇体内或特定细胞类型中的绝大多数DUB对果蝇的发育、成年运动性或寿命产生了巨大的影响。特定的DUB亚类被证明是特别必要的发展过程中，而其他人是重要的成人。几个DUBs是必不可少的神经元或神经胶质细胞在发育阶段;敲除其他扰乱了体内稳态的泛素化蛋白质在成年苍蝇，或有不良影响的翅膀定位作为一个结果的神经元的要求。我们证明了DUB酶家族在完整动物中的生理意义，发现这个蛋白酶家族的成员之间几乎没有功能冗余，并为未来的研究提供了见解，以了解DUB生物学在分子，细胞和生物体水平。
Deubiquitinating enzymes (DUBs) are proteases that control the post-translational modification of proteins by ubiquitin and in turn regulate diverse cellular pathways. Despite a growing understanding of DUB biology at the structural and molecular level, little is known about the physiological importance of most DUBs. Here, we systematically identify DUBs encoded by the genome of Drosophila melanogaster and examine their physiological importance in vivo. Through domain analyses we uncovered 41 Drosophila DUBs, most of which have human orthologues. Systematic knockdown of the vast majority of DUBs throughout the fly or in specific cell types had dramatic consequences for Drosophila development, adult motility or longevity. Specific DUB subclasses proved to be particularly necessary during development, while others were important in adults. Several DUBs were indispensable in neurons or glial cells during developmental stages; knockdown of others perturbed the homeostasis of ubiquitinated proteins in adult flies, or had adverse effects on wing positioning as a result of neuronal requirements. We demonstrate the physiological significance of the DUB family of enzymes in intact animals, find that there is little functional redundancy among members of this family of proteases, and provide insight for future investigations to understand DUB biology at the molecular, cellular and organismal levels.
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DOI：
10.1523/jneurosci.2635-09.2009
发表时间：
2009-09-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen PC;Qin LN;Li XM;Walters BJ;Wilson JA;Mei L;Wilson SM
通讯作者：
Wilson SM
影响因子：
16
作者：
Scaglione KM;Zavodszky E;Todi SV;Patury S;Xu P;Rodríguez-Lebrón E;Fischer S;Konen J;Djarmati A;Peng J;Gestwicki JE;Paulson HL
通讯作者：
Paulson HL
影响因子：
4
作者：
Clague, Michael J.;Coulson, Judy M.;Urbe, Sylvie
通讯作者：
Urbe, Sylvie
影响因子：
5.3
作者：
Crimmins, Stephen;Jin, Youngam;Wilson, Scott M.
通讯作者：
Wilson, Scott M.
影响因子：
64.8
作者：
Brummelkamp, TR;Nijman, SMB;Bernards, R
通讯作者：
Bernards, R