Home > Publications Database > Evolutionary Loss of Activity in De-Ubiquitylating Enzymes of the OTU Family. > print

001     138234
005     20240321220409.0
024 7 _ |a 10.1371/journal.pone.0143227
|2 doi
024 7 _ |a pmid:26588485
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024 7 _ |a pmc:PMC4654579
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037 _ _ |a DZNE-2020-04556
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Louis, Marcell
|0 P:(DE-2719)2810402
|b 0
|e First author
245 _ _ |a Evolutionary Loss of Activity in De-Ubiquitylating Enzymes of the OTU Family.
260 _ _ |a San Francisco, California, US
|c 2015
|b PLOS
264 _ 1 |3 online
|2 Crossref
|b Public Library of Science (PLoS)
|c 2015-11-20
336 7 _ |a article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a Understanding function and specificity of de-ubiquitylating enzymes (DUBs) is a major goal of current research, since DUBs are key regulators of ubiquitylation events and have been shown to be mutated in human diseases. Most DUBs are cysteine proteases, relying on a catalytic triad of cysteine, histidine and aspartate to cleave the isopeptide bond between two ubiquitin units in a poly-ubiquitin chain. We have discovered that the two Drosophila melanogaster homologues of human OTUD4, CG3251 and Otu, contain a serine instead of a cysteine in the catalytic OTU (ovarian tumor) domain. DUBs that are serine proteases instead of cysteine- or metallo-proteases have not been described. In line with this, neither CG3251 nor Otu protein were active to cleave ubiquitin chains. Re-introduction of a cysteine in the catalytic center did not render the enzymes active, indicating that further critical features for ubiquitin binding or cleavage have been lost in these proteins. Sequence analysis of OTUD4 homologues from various other species showed that within this OTU subfamily, loss of the catalytic cysteine has occurred frequently in presumably independent events, as well as gene duplications or triplications, suggesting DUB-independent functions of OTUD4 proteins. Using an in vivo RNAi approach, we show that CG3251 might function in the regulation of Inhibitor of Apoptosis (IAP)-antagonist-induced apoptosis, presumably in a DUB-independent manner.
536 _ _ |a 341 - Molecular Signaling (POF3-341)
|0 G:(DE-HGF)POF3-341
|c POF3-341
|f POF III
|x 0
542 _ _ |i 2015-11-20
|2 Crossref
|u http://creativecommons.org/licenses/by/4.0/
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Drosophila Proteins
|2 NLM Chemicals
650 _ 7 |a Inhibitor of Apoptosis Proteins
|2 NLM Chemicals
650 _ 7 |a RNA, Small Interfering
|2 NLM Chemicals
650 _ 7 |a Ubiquitin
|2 NLM Chemicals
650 _ 7 |a otu protein, Drosophila
|2 NLM Chemicals
650 _ 7 |a Serine
|0 452VLY9402
|2 NLM Chemicals
650 _ 7 |a OTUD4 protein, human
|0 EC 3.4.19.12
|2 NLM Chemicals
650 _ 7 |a Ubiquitin-Specific Proteases
|0 EC 3.4.19.12
|2 NLM Chemicals
650 _ 7 |a Cysteine
|0 K848JZ4886
|2 NLM Chemicals
650 _ 2 |a Amino Acid Sequence
|2 MeSH
650 _ 2 |a Amino Acid Substitution
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Apoptosis: genetics
|2 MeSH
650 _ 2 |a Binding Sites
|2 MeSH
650 _ 2 |a Catalytic Domain
|2 MeSH
650 _ 2 |a Conserved Sequence
|2 MeSH
650 _ 2 |a Cysteine: metabolism
|2 MeSH
650 _ 2 |a Drosophila Proteins: genetics
|2 MeSH
650 _ 2 |a Drosophila Proteins: metabolism
|2 MeSH
650 _ 2 |a Drosophila melanogaster: genetics
|2 MeSH
650 _ 2 |a Drosophila melanogaster: metabolism
|2 MeSH
650 _ 2 |a Evolution, Molecular
|2 MeSH
650 _ 2 |a Gene Expression Regulation
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Inhibitor of Apoptosis Proteins: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Inhibitor of Apoptosis Proteins: genetics
|2 MeSH
650 _ 2 |a Inhibitor of Apoptosis Proteins: metabolism
|2 MeSH
650 _ 2 |a Molecular Sequence Data
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a RNA, Small Interfering: genetics
|2 MeSH
650 _ 2 |a RNA, Small Interfering: metabolism
|2 MeSH
650 _ 2 |a Sequence Alignment
|2 MeSH
650 _ 2 |a Sequence Homology, Amino Acid
|2 MeSH
650 _ 2 |a Serine: metabolism
|2 MeSH
650 _ 2 |a Ubiquitin: genetics
|2 MeSH
650 _ 2 |a Ubiquitin: metabolism
|2 MeSH
650 _ 2 |a Ubiquitin-Specific Proteases: genetics
|2 MeSH
650 _ 2 |a Ubiquitin-Specific Proteases: metabolism
|2 MeSH
650 _ 2 |a Ubiquitination
|2 MeSH
700 1 _ |a Hofmann, Kay
|0 P:(DE-HGF)0
|b 1
700 1 _ |a Broemer, Meike
|0 P:(DE-2719)2810307
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|e Last author
773 1 8 |a 10.1371/journal.pone.0143227
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773 _ _ |a 10.1371/journal.pone.0143227
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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913 1 _ |a DE-HGF
|b Forschungsbereich Gesundheit
|l Erkrankungen des Nervensystems
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|2 Crossref
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