UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself.
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.
Wada
Keiji
K
Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Kamitani
Tetsu
T
D002460:Cell Line; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D000099207:SS-A Antigen
D010450:Endopeptidases; D005656:Fungal Proteins; D020929:Mitogen-Activated Protein Kinase Kinases; D015513:Oncogene Proteins; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors; D012261:Ribonucleoproteins; D025801:Ubiquitin; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D000099207:SS-A Antigen; C486203:USP4 protein, human; C414539:MAP kinase kinase ubc5; C438343:UnpEL enzyme