Abstract
The autoantigen Ro52 is an E3 ubiquitin ligase that can ubiquitinate itself (self-ubiquitination). Recently, we showed that UnpEL/Usp4 is an isopeptidase that can deconjugate ubiquitin from self-ubiquitinated Ro52. Here, we showed that UnpEL is ubiquitinated by Ro52 in cooperation with UbcH5B in vitro. We also showed that UnpEL is ubiquitinated by Ro52 in HEK293T cells. Interestingly, a catalytically inactive UnpEL mutant was strongly ubiquitinated by Ro52 in HEK293T cells. These results suggest that wild-type UnpEL is ubiquitinated by Ro52 and deubiquitinated by itself (self-deubiquitination), while mutant UnpEL is ubiquitinated by Ro52 but not deubiquitinated by itself. In conclusion, Ro52 and UnpEL transregulate each other by ubiquitination and deubiquitination.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Cell Line
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Endopeptidases / genetics
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Endopeptidases / metabolism*
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Fungal Proteins
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Humans
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mutation / genetics
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Proteasome Endopeptidase Complex / metabolism
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Proteasome Inhibitors
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Protein Binding
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism*
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Ubiquitin / metabolism*
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Ubiquitin Thiolesterase
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Ubiquitin-Specific Proteases
Substances
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Fungal Proteins
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Oncogene Proteins
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Proteasome Inhibitors
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Ribonucleoproteins
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SS-A antigen
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USP4 protein, human
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Ubiquitin
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MAP kinase kinase ubc5
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Mitogen-Activated Protein Kinase Kinases
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Endopeptidases
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Ubiquitin Thiolesterase
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Ubiquitin-Specific Proteases
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Proteasome Endopeptidase Complex
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UnpEL enzyme