Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSA.
Ubiquitylation appears to be involved in the membrane trafficking system including endocytosis, exocytosis, and ER-to-Golgi transport. We found that PIRH2, which was identified as an interacting protein for androgen receptor or p53, interacts with and ubiquitylates the epsilon-subunit of coatmer complex, epsilon-COP. PIRH2 promotes the ubiquitylation of epsilon-COP in vitro and in vivo and consequently promotes the degradation of epsilon-COP. The interaction between PIRH2 and epsilon-COP is affected by the presence of androgen, and PIRH2 in the presence of androgen promotes ubiquitylation of epsilon-COP in vivo. Furthermore, overexpression of the wild type of PIRH2 in prostate cancer cells causes downregulation of the secretion of prostate-specific antigen (PSA), a secretory protein in prostate epithelial cells and one of diagnostic markers for prostate cancer. Our results indicate that PIRH2 functions as a regulator for COP I complex.
Maruyama
Satoru
S
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
Miyajima
Naoto
N
Bohgaki
Miyuki
M
Tsukiyama
Tadasuke
T
Shigemura
Masahiko
M
Nonomura
Katsuya
K
Hatakeyama
Shigetsugu
S
D000728:Androgens / Q000494:pharmacology; D002478:Cells, Cultured; D020755:Coat Protein Complex I / Q000378:metabolism / Q000502:physiology; D020756:Coatomer Protein / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008954:Models, Biological; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D000728:Androgens; D020755:Coat Protein Complex I; D020756:Coatomer Protein; D013196:Dihydrotestosterone; C485369:RCHY1 protein, human; D044767:Ubiquitin-Protein Ligases; D017430:Prostate-Specific Antigen