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
Article

Abstract

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.

Keywords

PIRH2 ε-COP Ubiquitin Androgen receptor PSA 

Notes

Acknowledgments

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.

References

  1. 1.
    Gelmann EP (2002) Molecular biology of the androgen receptor. J Clin Oncol 20:3001–3015PubMedCrossRefGoogle Scholar
  2. 2.
    Nessler-Menardi C, Jotova I, Culig Z, Eder IE, Putz T, Bartsch G, Klocker H (2000) Expression of androgen receptor coregulatory proteins in prostate cancer and stromal-cell culture models. Prostate 45:124–131PubMedCrossRefGoogle Scholar
  3. 3.
    Gregory CW, He B, Johnson RT, Ford OH, Mohler JL, French FS, Wilson EM (2001) A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer Res 61:4315–4319PubMedGoogle Scholar
  4. 4.
    Fujimoto N, Mizokami A, Harada S, Matsumoto T (2001) Different expression of androgen receptor coactivators in human prostate. Urol 58:289–294PubMedCrossRefGoogle Scholar
  5. 5.
    Saporita AJ, Zhang Q, Navai N, Dincer Z, Hahn J, Cai X, Wang Z (2003) Identification and characterization of a ligand-regulated nuclear export signal in androgen receptor. J Biol Chem 278:41998–42005PubMedCrossRefGoogle Scholar
  6. 6.
    Suzuki H, Ueda T, Ichikawa T, Ito H (2003) Androgen receptor involvement in the progression of prostate cancer. Endocr Relat Cancer 10:209–216PubMedCrossRefGoogle Scholar
  7. 7.
    Beitel LK, Elhaji YA, Lumbroso R, Wing SS, Panet-Raymond V, Gottlieb B, Pinsky L, Trifiro MA (2002) Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity. J Mol Endocrinol 29:41–60PubMedCrossRefGoogle Scholar
  8. 8.
    Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant JM, Lozano G, Hakem R, Benchimol S (2003) Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 112:779–791PubMedCrossRefGoogle Scholar
  9. 9.
    Zhang L, Li J, Wang C, Ma Y, Huo K (2005) A new human gene hNTKL-BP1 interacts with hPirh2. Biochem Biophys Res Commun 330:293–297PubMedCrossRefGoogle Scholar
  10. 10.
    Logan IR, Gaughan L, McCracken SR, Sapountzi V, Leung HY, Robson CN (2006) Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer. Mol Cell Biol 26:6502–6510PubMedCrossRefGoogle Scholar
  11. 11.
    Ostermann J, Orci L, Tani K, Amherdt M, Ravazzola M, Elazar Z, Rothman JE (1993) Stepwise assembly of functionally active transport vesicles. Cell 75:1015–1025PubMedCrossRefGoogle Scholar
  12. 12.
    Rothman JE (1994) Mechanisms of intracellular protein transport. Nature 372:55–63PubMedCrossRefGoogle Scholar
  13. 13.
    Lanoix J, Ouwendijk J, Stark A, Szafer E, Cassel D, Dejgaard K, Weiss M, Nilsson T (2001) Sorting of Golgi resident proteins into different subpopulations of COPI vesicles: a role for ArfGAP1. J Cell Biol 155:1199–1212PubMedCrossRefGoogle Scholar
  14. 14.
    Lee SY, Yang JS, Hong W, Premont RT, Hsu VW (2005) ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation. J Cell Biol 168:281–290PubMedCrossRefGoogle Scholar
  15. 15.
    Schledzewski K, Brinkmann H, Mendel RR (1999) Phylogenetic analysis of components of the eukaryotic vesicle transport system reveals a common origin of adaptor protein complexes 1, 2, and 3 and the F subcomplex of the coatomer COPI. J Mol Evol 48:770–778PubMedCrossRefGoogle Scholar
  16. 16.
    Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479PubMedCrossRefGoogle Scholar
  17. 17.
    Scheffner M, Nuber U, Huibregtse JM (1995) Protein ubiquitination involving an E1-E2-E3 enzyme ubiquitin thioester cascade. Nature 373:81–83PubMedCrossRefGoogle Scholar
  18. 18.
    Hershko A, Heller H, Elias S, Ciechanover A (1983) Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem 258:8206–8214PubMedGoogle Scholar
  19. 19.
    Huibregtse JM, Scheffner M, Beaudenon S, Howley PM (1995) A family of proteins structurally and functionally related to the E6–AP ubiquitin-protein ligase. Proc Natl Acad Sci USA 92:2563–2567PubMedCrossRefGoogle Scholar
  20. 20.
    Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM (1999) RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci USA 96:11364–11369PubMedCrossRefGoogle Scholar
  21. 21.
    Freemont PS (2000) RING for destruction? Curr Biol 10:R84–R87PubMedCrossRefGoogle Scholar
  22. 22.
    Joazeiro CA, Weissman AM (2000) RING finger proteins: mediators of ubiquitin ligase activity. Cell 102:549–552PubMedCrossRefGoogle Scholar
  23. 23.
    Hatakeyama S, Yada M, Matsumoto M, Ishida N, Nakayama KI (2001) U box proteins as a new family of ubiquitin-protein ligases. J Biol Chem 276:33111–33120PubMedCrossRefGoogle Scholar
  24. 24.
    Hicke L (2001) A new ticket for entry into budding vesicles-ubiquitin. Cell 106:527–530PubMedCrossRefGoogle Scholar
  25. 25.
    Sufrin G, Coffey DS (1976) Flutamide. Mechanism of action of a new nonsteroidal antiandrogen. Invest Urol 13:429–434PubMedGoogle Scholar
  26. 26.
    Oesterling JE (1991) Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol 145:907–923PubMedGoogle Scholar
  27. 27.
    Catalona WJ, Smith DS, Ratliff TL, Dodds KM, Coplen DE, Yuan JJ, Petros JA, Andriole GL (1991) Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 324:1156–1161PubMedCrossRefGoogle Scholar
  28. 28.
    Husmann DA, Wilson CM, McPhaul MJ, Tilley WD, Wilson JD (1990) Antipeptide antibodies to two distinct regions of the androgen receptor localize the receptor protein to the nuclei of target cells in the rat and human prostate. Endocrinology 126:2359–2368PubMedCrossRefGoogle Scholar
  29. 29.
    Tyagi RK, Lavrovsky Y, Ahn SC, Song CS, Chatterjee B, Roy AK (2000) Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand-activated androgen receptor in living cells. Mol Endocrinol 14:1162–1174PubMedCrossRefGoogle Scholar
  30. 30.
    Hata S, Koyama S, Kawahara H, Doi N, Maeda T, Toyama-Sorimachi N, Abe K, Suzuki K, Sorimachi H (2006) Stomach-specific calpain, nCL-2, localizes in mucus cells and proteolyzes the beta-subunit of coatomer complex, beta-COP. J Biol Chem 281:11214–11224PubMedCrossRefGoogle Scholar
  31. 31.
    Riegman PH, Vlietstra RJ, van der Korput JA, Brinkmann AO, Trapman J (1991) The promoter of the prostate-specific antigen gene contains a functional androgen responsive element. Mol Endocrinol 5:1921–1930PubMedCrossRefGoogle Scholar
  32. 32.
    Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, Trapman J (1996) Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem 271:6379–6388PubMedCrossRefGoogle Scholar
  33. 33.
    Gaughan L, Logan IR, Cook S, Neal DE, Robson CN (2002) Tip60 and histone deacetylase 1 regulate androgen receptor activity through changes to the acetylation status of the receptor. J Biol Chem 277:25904–25913PubMedCrossRefGoogle Scholar
  34. 34.
    Johnson JL, Ellis BA, Noack D, Seabra MC, Catz SD (2005) The Rab27a-binding protein, JFC1, regulates androgen-dependent secretion of prostate-specific antigen and prostatic-specific acid phosphatase. Biochem J 391:699–710PubMedCrossRefGoogle Scholar
  35. 35.
    Logan IR, Sapountzi V, Gaughan L, Neal DE, Robson CN (2004) Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome. J Biol Chem 279:11696–11704PubMedCrossRefGoogle Scholar
  36. 36.
    Duan W, Gao L, Druhan LJ, Zhu WG, Morrison C, Otterson GA, Villalona-Calero MA (2004) Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer. J Natl Cancer Inst 96:1718–1721PubMedCrossRefGoogle Scholar
  37. 37.
    Debes JD, Tindall DJ (2004) Mechanisms of androgen-refractory prostate cancer. N Engl J Med 351:1488–1490PubMedCrossRefGoogle Scholar
  38. 38.
    Di Lorenzo G, De Placido S (2006) Hormone refractory prostate cancer (HRPC): present and future approaches of therapy. Int J Immunopathol Pharmacol 19:11–34PubMedGoogle Scholar
  39. 39.
    Aihara M, Lebovitz RM, Wheeler TM, Kinner BM, Ohori M, Scardino PT (1994) Prostate specific antigen and gleason grade: an immunohistochemical study of prostate cancer. J Urol 151:1558–1564PubMedGoogle Scholar

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

Personalised recommendations