Skip to main content
SpringerLink
Log in

Rpn4p is a positive and negative transcriptional regulator of the ubiquitin-proteasome system

  • Cell Molecular Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

In eukaryotes, the ubiquitin-proteasome proteolytic system is involved in metabolizing most of cell proteins and in major regulation pathways. Although its structure and functioning are fairly well studied, little is known about the regulation of gene expression in this system. The regulation of proteasome gene expression has been described only for Saccharomyces cerevisiae and includes the proteasome-associated transcription factor Rpn4p and its binding site, the proteasome-associated control element (PACE). There are two questions concerning the role of Rpn4p as a transcription factor: whether Rpn4p regulates the PACE-containing genes of the protein ubiquitination system and what contribution Rpn4p makes to the stress-induced changes in proteasome mRNA levels. Semiquantitative RT-PCR showed that deletion of S. cerevisiae RPN4 decreased the RAD6, RAD23, and CDC48 mRNA levels, while the UBI4 mRNA level increased. Stress factors, such as heat shock or the alkylating agent methyl methanesulfonate, induced Rpn4p-dependent transcriptional upregulation of RPT4 and RPN5. At the same time, methyl methanesulfonate downregulated the CDC48 expression in the wild-type strain. Apparently, Rpn4p acts both as an activator and a repressor of transcription of the ubiquitinproteasome genes under normal and stress conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Voges D., Zwickl P., Baumeister W. 1999. The 26S proteasome: A molecular machine designed for controlled proteolysis. Annu. Rev. Biochem. 68, 1015–1068.

    Article  PubMed  CAS  Google Scholar 

  2. Coux O., Tanaka K., Goldberg A.L. 1996. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65, 801–847.

    Article  PubMed  CAS  Google Scholar 

  3. Hershko A., Ciechanover A. 1998. The ubiquitin system. Annu. Rev. Biochem. 67, 425–479.

    Article  PubMed  CAS  Google Scholar 

  4. Varshavsky A. 1997. The ubiquitin system. Trends Biochem. Sci. 22, 383–387.

    Article  PubMed  CAS  Google Scholar 

  5. Schubert U., Anton L.C., Gibbs J., Norbury C.C., Yewdell J.W., Bennink J.R. 2000. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature. 404, 770–774.

    Article  PubMed  CAS  Google Scholar 

  6. Ferrel K., Wilkinson C.R., Dubiel W., Gordon C. 2000. Regulatory subunit interactions of the 26S proteasome, a complex problem. Trends Cell Biol. 25, 83–88.

    Google Scholar 

  7. Baboshina O.V., Haas A.L. 1996. Novel multiubiquitin chain linkages catalyzed by the conjugating enzymes E2-EPF and RAD6 are recognized by the 26S proteasome subunit 5. J. Biol. Chem. 271, 2823–2831.

    Article  PubMed  CAS  Google Scholar 

  8. Thrower J.S., Hoffman L., Rechsteiner M., Pickart C. 2000. Recognition of the polyubiquitin proteolytic signal. EMBO J. 19, 94–102.

    Article  PubMed  CAS  Google Scholar 

  9. Glickmann M., Rubin D.M., Coux O., Wefes I., Pfeifer G., Cjeka Z., Baumaister W., Fried V.A., Finley D. 1998. A subcomplex of the proteasome regulator particle required for ubiquitin-conjugate degradation and related to the COP9-Signalosome and eIF3. Cell. 94, 615–623.

    Article  Google Scholar 

  10. Lam Y., Lowson T.G., Velayutham M., Zweier J.L., Pickart C.M. 2002. A protaasomal ATPase subunit recognizes the polyubiquitin degradation signal. Nature. 18, 763–767.

    Article  Google Scholar 

  11. Verma R., Aravind L., Oania R., McDonald W.H., Yates J.R., Koonin E.V., Deshaies R.J. 2002. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science. 298, 611–615.

    Article  PubMed  CAS  Google Scholar 

  12. Groll M., Ditzel L., Lowe J., Stock D., Bochtler M., Bartunik H.D., Huber R. 1997. Structure of 20S proteasome from yeast at a 2.4 Å resolution. Nature. 386, 463–471.

    Article  PubMed  CAS  Google Scholar 

  13. Lowe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R. 1995. Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 Å resolution. Science. 268, 533–539.

    Article  PubMed  CAS  Google Scholar 

  14. Mannhaupt G., Schnall R., Karpov V., Vetter I., Feldmann H. 1999. Rpn4 acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast. FEBS Lett. 450, 27–34.

    Article  PubMed  CAS  Google Scholar 

  15. Kapranov A.B., Kuryatova M.V., Preobrazhenskaya O.V., Tutyaeva V.V., Stucka R., Feldmann H., Karpov V.L. 2001. Isolation and identification of PACE-binding protein Rpn4, a new transcriptional activator regulating 26S-proteasomal and other genes. Mol. Biol. 35, 420–431.

    Article  CAS  Google Scholar 

  16. Fujimuro M., Tanaka K., Yokosawa H., Toh-e A. 1998. Son1p is a component of the 26S proteasome of the yeast Saccharomyces cerevisiae. FEBS Lett. 423, 149–154.

    Article  PubMed  CAS  Google Scholar 

  17. Glickman M.H., Ciechanover A. 2002. Ubiquitin-proteasome proteolytic pathway: Destruction for the sake of construction. Physiol. Rev. 82, 373–428.

    PubMed  CAS  Google Scholar 

  18. Prinz S., Avila-Campillo I., Aldridge C., Srinivasan A., Dimitrov K., Siegel A.F., Galitski T. 2004. Control of yeast filamentous-form growth by modules in an integrated molecular network. Genome Res. 14, 380–390.

    Article  PubMed  CAS  Google Scholar 

  19. Xie Y., Varshavsky A. 2001. RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: A negative feedback circuit. Proc. Natl. Acad. Sci. USA. 98, 3056–3061.

    Article  PubMed  CAS  Google Scholar 

  20. Nelson M.K., Kurihara T., Silver P.A. 1993. Extragenic suppressors of mutations in the cytoplasmic C terminus of Sec63 define five genes in Saccharomyces cerevisae. Genetics. 134, 159–173 nerevisae. Genetics J. 134, 159–173.

    PubMed  CAS  Google Scholar 

  21. Johnston E. 1995. A proteolytic pathway that recognizes ubiquitin as a degradation signal. J. Biol. Chem. 270, 17442–17456.

    Article  Google Scholar 

  22. Ng D.T., Spear E.D., Walter P. 2000. The unfolded protein response regulates multiple aspects of secretory and membrane protein biogenesis and endoplasmic reticulum quality control. J. Cell Biol. 150, 77–88.

    Article  PubMed  CAS  Google Scholar 

  23. Ju D., Wang L., Mao X., Xie Y. 2004. Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit. Biochem. Biophys. Res. Commun. 321, 51–57.

    Article  PubMed  CAS  Google Scholar 

  24. London M.K., Keck B.I., Ramos P.C., Dohmen R.J. 2004. Regulatory mechanisms controlling biogenesis of ubiquitin and the proteasome. FEBS Lett. 567, 259–264.

    Article  PubMed  CAS  Google Scholar 

  25. Owsianik G., Balzil L., Ghislain M. 2002. Control of 26S proteasome expression by transcription factors regulating multidrug resistance in Saccharomyces cerevisiae. Mol. Microbiol. 43, 1295–1308.

    Article  PubMed  CAS  Google Scholar 

  26. Hahn J.S., Neef D.W., Thiele D.J. 2006. A stress regulatory network for co-ordinated activation of proteasome expression mediated by yeast heat shock transcription factor. Mol. Microbiol. 60, 240–251.

    Article  PubMed  CAS  Google Scholar 

  27. Schmitt M.E., Brown T.A., Trumpower B.L. 1990. A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae. Nucleic Acids Res. 18, 3091–3092.

    Article  PubMed  CAS  Google Scholar 

  28. Jelinsky S.A., Estep P., Church G.M., Samson L.D. 2000. Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes. Mol. Cell. Biol. 20, 8157–8167.

    Article  PubMed  CAS  Google Scholar 

  29. Sung P., Berleth E., Pickart C., Prakash S., Prakash L. 1991. Yeast RAD6 encoded ubiquitin conjugating enzyme mediates protein degradation dependent on the N-end-recognizing E3 enzyme. EMBO J. 10, 2187–2193.

    PubMed  CAS  Google Scholar 

  30. Prakash S., Sung P., Prakash L. 1993. DNA repair genes and proteins of Saccharomyces cerevisiae. Annu. Rev. Genet. 27, 33–70.

    Article  PubMed  CAS  Google Scholar 

  31. Jelinsky S.A., Leona D.S. 1999. Global response of Saccharomyces cerevisiae to an alkylating agent. Proc. Natl. Acad. Sci. USA. 96, 1486–1491.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia

    D. S. Karpov, S. A. Osipov, O. V. Preobrazhenskaya & V. L. Karpov

Authors
  1. D. S. Karpov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. A. Osipov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. V. Preobrazhenskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. L. Karpov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D. S. Karpov.

Additional information

Original Russian Text © D.S. Karpov, S.A. Osipov, O.V. Preobrazhenskaya, V.L. Karpov, 2008, published in Molekulyarnaya Biologiya, 2008, Vol. 42, No. 3, pp. 518–525.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karpov, D.S., Osipov, S.A., Preobrazhenskaya, O.V. et al. Rpn4p is a positive and negative transcriptional regulator of the ubiquitin-proteasome system. Mol Biol 42, 456–462 (2008). https://doi.org/10.1134/S0026893308030151

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893308030151

Key words

Search

Navigation