Ro52 functionally interacts with IgG1 and regulates its quality control via the ERAD system.
The 52-kDa form of SSA/Ro protein (Ro52) is one of autoantigens associated with autoimmune disorders such as systemic lupus erythematosus and Sjögren's syndrome. Anti-SSA/Ro antibodies, the biological function of which remains unknown, are frequently found in the serum of these patients. Recent functional genomic approaches have shown that Ro52/TRIM21 is one of the TRIM family proteins with a RING-finger domain which is closely associated with E3 ubiquitin ligase activity. We found by using yeast-two hybrid screening that Ro52 has an E3 activity in vitro and interacts with human IgG1 heavy chain. We also found that IgG1 heavy chain was modified with polyubiquitination by Ro52 and degraded through the ubiquitin-proteasome system in mammalian cells. Our results also showed that Ro52 interacts with the molecular chaperone p97/VCP, which is thought to function in the endoplasmic reticulum associated degradation (ERAD) system. It is likely that Ro52 plays a role in proteasomal degradation of unfolded IgG1, which is retrogradely transferred from the endoplasmic reticulum to the cytosol. Taken together, our findings suggest that Ro52 plays a significant role in quality control of IgG1 through the ERAD system.
Takahata
Mutsumi
M
Department of Biochemistry, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Bohgaki
Miyuki
M
Tsukiyama
Tadasuke
T
Kondo
Takeshi
T
Asaka
Masahiro
M
Hatakeyama
Shigetsugu
S
D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G / Q000378:metabolism*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D054829:RING Finger Domains; D000071701:Regulatory Factor X Transcription Factors; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination; D000074405:Valosin Containing Protein; D000099207:SS-A Antigen
D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex; D000071701:Regulatory Factor X Transcription Factors; D012261:Ribonucleoproteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000074405:Valosin Containing Protein; D000099207:SS-A Antigen; C000614178:VCP protein, human