气候变化领域集成服务门户(CCPortal): Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases

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DOI	10.1073/pnas.2006947118
	Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases
	de Cesare V.; Lopez D.C.; Mabbitt P.D.; Fletcher A.J.; Soetens M.; Antico O.; Wood N.T.; Virdee S.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct, and its physiological importance is emerging. Here, we couple chemically and chemoenzymatically synthesized ubiquitinated lysine and threonine model substrates to a mass spectrometry-based DUB assay. Using this platform, we profile two-thirds of known catalytically active DUBs for threonine esterase and lysine isopeptidase activity and find that most DUBs demonstrate dual selectivity. However, with two anomalous exceptions, the ovarian tumor domain DUB class demonstrates specific (iso)peptidase activity. Strikingly, we find the Machado–Joseph disease (MJD) class to be unappreciated non-lysine DUBs with highly specific ubiquitin esterase activity rivaling the efficiency of the most active isopeptidases. Esterase activity is dependent on the canonical catalytic triad, but proximal hydrophobic residues appear to be general determinants of non-lysine activity. Our findings also suggest that ubiquitin esters have appreciable cellular stability and that nonlysine ubiquitination is an integral component of the ubiquitin system. Its regulatory sophistication is likely to rival that of canonical ubiquitination. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DUBs; Non-lysine ubiquitination; Ubiquitin
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180865
作者单位	Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, Scotland, DD1 5EH, United Kingdom
推荐引用方式 GB/T 7714	de Cesare V.,Lopez D.C.,Mabbitt P.D.,et al. Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases[J],2021,118(4).
APA	de Cesare V..,Lopez D.C..,Mabbitt P.D..,Fletcher A.J..,Soetens M..,...&Virdee S..(2021).Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	de Cesare V.,et al."Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).