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.
Department of Cardiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Keiji
K
Wada
Tetsu
T
Kamitani
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