Molecular and Cellular Biochemistry

, Volume 307, Issue 1–2, pp 73–82 | Cite as

Ubiquitylation of ε-COP by PIRH2 and regulation of the secretion of PSA

  • Satoru Maruyama
  • Naoto Miyajima
  • Miyuki Bohgaki
  • Tadasuke Tsukiyama
  • Masahiko Shigemura
  • Katsuya Nonomura
  • Shigetsugu Hatakeyama


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 ε-subunit of coatmer complex, ε-COP. PIRH2 promotes the ubiquitylation of ε-COP in vitro and in vivo and consequently promotes the degradation of ε-COP. The interaction between PIRH2 and ε-COP is affected by the presence of androgen, and PIRH2 in the presence of androgen promotes ubiquitylation of ε-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.


PIRH2 ε-COP Ubiquitin Androgen receptor PSA 



We thank G. Sobue and T. Kitamura for the plasmids and cell lines and Y. Soida for helping with the preparation of the manuscript. The work was supported in part by a research grant from Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology (18013001), the Osaka Cancer Research Foundation and the Akiyama Foundation.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Satoru Maruyama
    • 1
    • 2
  • Naoto Miyajima
    • 1
    • 2
  • Miyuki Bohgaki
    • 1
  • Tadasuke Tsukiyama
    • 1
  • Masahiko Shigemura
    • 3
  • Katsuya Nonomura
    • 2
  • Shigetsugu Hatakeyama
    • 1
  1. 1.Department of BiochemistryHokkaido University Graduate School of MedicineSapporoJapan
  2. 2.Department of UrologyHokkaido University Graduate School of MedicineSapporoJapan
  3. 3.Clinical LaboratoryHokkaido University HospitalSapporoJapan

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