Skip to main content
SpringerLink
Log in

Expression regulation of the proteasomal genes in eukaryotes

  • To the Anniversary of the Institute of Molecular Biology
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

The ubiquitin-proteasome system (UPS) is involved in the degradation of many intracellular proteins and is necessary for a proper functioning of the cell under normal conditions and its survival in stress. This review considers the general principles of the structure and functioning of the UPS. Main attention is paid to the expression regulation of the proteasomal genes in yeasts and structural and functional analyses of the Rpn4p transcription factor, which activates the proteasomal genes in Saccharomyces cerevisiae. Data on the regulation of proteasomal gene expression in higher eukaryotes are discussed.

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. Varshavsky A. 1996. The N-end rule: Functions, mysteries, uses. Proc. Natl. Acad. Sci. USA. 93, 12142–12149.

    Article  PubMed  CAS  Google Scholar 

  2. Rogers S., Wells R., Rechstiener M. 1986. Amino acid sequences common to rapidly degraded proteins: The PEST hypothesis. Science. 234, 364–368.

    Article  PubMed  CAS  Google Scholar 

  3. Yamano H., Gannon J., Hunt T. 1996. The role of proteolysis in cell cycle progression in Schizosaccharomyces pombe. EMBO J. 15, 5268–5279.

    PubMed  CAS  Google Scholar 

  4. Murata S., Minami Y., Minami M., Chiba T., Tanaka K. 2001. CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2, 1133–1138.

    Article  PubMed  CAS  Google Scholar 

  5. Molinari M., Milner J. 1995. p53 in complex with DNA is resistant to ubiquitin-dependent proteolysis in the presence of HPV-16 E6. Oncogene. 10, 1849–1854.

    PubMed  CAS  Google Scholar 

  6. Scheffner M., Huibregste J., Vierstra R.D., Howley P.M. 1993. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell. 75, 495–505.

    Article  PubMed  CAS  Google Scholar 

  7. Pickart C.M. 2001. Mechanisms underlying ubiquitination. Annu. Rev. Biochem. 70, 503–533.

    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. Ozkaynak E., Finley D., Solomon M.J., Varshavky A. 1987. The yeast ubiquitin genes: A family of natural gene fusions. EMBO J. 6, 1429–1439.

    PubMed  CAS  Google Scholar 

  10. Hatakeyama S., Yada M., Matsumoto M., Ishida N., Nakayama K. 2001. U box proteins as a new family of ubiquitin-protein ligases. J. Biol. Chem. 276, 33111–33120.

    Article  PubMed  CAS  Google Scholar 

  11. D’Andrea A., Pellman D. 1998. Deubiquitinating enzymes: A new class of biological regulators. Crit. Rev. Biochem. Mol. Biol. 33, 337–352.

    Article  PubMed  Google Scholar 

  12. Deveraux Q., Ustrell V., Pickart C., Rechsteiner M. 1994. A 26S protease subunits that binds ubiquitin conjugates. J. Biol. Chem. 269, 7059–7061.

    PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  14. Cagney G., Uetz P., Fields S. 2001. Two-hybrid analysis of the Saccharomyces cerevisiae 26S proteasome. Physiol. Genomics. 7, 27–34.

    PubMed  CAS  Google Scholar 

  15. 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 

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

    Article  PubMed  CAS  Google Scholar 

  17. Orlowski M. 1990. The multicatalitic proteinase complex: A major extralysosomal proteolytic system. Biochemistry. 29, 10289–10297.

    Article  PubMed  CAS  Google Scholar 

  18. 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 

  19. Kapranov A.B., Kuryatova M.V., Preobrazhenskaya O.V., Tyutyaeva 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 

  20. 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 

  21. 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.

    PubMed  CAS  Google Scholar 

  22. Johnston E., Ma C., Ota M., Varshavsky A. 1995. A proteolytic pathway that recognizes ubiquitin as a degradation signal. J. Biol. Chem. 270, 17442–17456.

    Article  Google Scholar 

  23. Yokota K., Kagawa S., Shimizu Y., Akioka H., Tsurumi C., Noda C., Fujimuro M., Yokosawa H., Fujiwara T., Takahashi E., Ohba M., Yamasaki M., DeMartino G.N., Slaughter C.A., Toh-e A., Tanaka K. 1996. cDNA cloning of p112, the largest regulatory subunit of the human 26s proteasome, and functional analysis of its yeast homologue, Sen3p. Mol. Biol. Cell. 7, 853–870.

    PubMed  CAS  Google Scholar 

  24. 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 

  25. Verma R., Chen S., Feldman R., Schieltz D., Yates J., Dohmen R.J., Deshaies R.J. 2000. Proteasomal proteomics: Identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol. Biol. Cell. 11, 3425–3439.

    PubMed  CAS  Google Scholar 

  26. Glickman M.H., Rubin D.M., Fried V.A., Finley D. 1998. The regulatory particle of the Saccharomyces cerevisiae proteasome. Mol. Cell Biol. 18, 3149–3162.

    PubMed  CAS  Google Scholar 

  27. 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 

  28. 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 

  29. 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 

  30. 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 

  31. 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 

  32. Ju D., Xie Y. 2004. Proteasomal degradation of RPN4 via two distinct mechanisms: Ubiquitin-dependent and — independent. J. Biol. Chem. 279, 23851–23854.

    Article  PubMed  CAS  Google Scholar 

  33. Ju D., Xie Y. 2006. Identification of the preferential ubiquitination site and ubiquitin-dependent degradation signal of Rpn4. J. Biol. Cell. 281, 10657–10662.

    CAS  Google Scholar 

  34. Wang L., Mao X., Ju D., Xie Y. 2004. Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase. J. Biol. Chem. 279, 55218–55223.

    Article  PubMed  CAS  Google Scholar 

  35. Ju D., Xu H., Wang, X., Xie Y. 2007. Ubiquitin-mediated degradation of Rpn4 is controlled by a phosphorylation-dependent ubiquitylation signal. Biochim. Biophys. Acta. 1773, 1672–1680.

    Article  PubMed  CAS  Google Scholar 

  36. Ju D., Wang, X., Xu H., Xie Y. 2008. Genome-wide analysis identifies MYND-domain protein Mub1 as an essential factor for Rpn4 ubiquitylation. Mol. Cell. Biol. 28, 1404–1412.

    Article  PubMed  CAS  Google Scholar 

  37. Karpov D.S., Osipov S.A., Preobrazhenskaya O.V., Karpov V.L. 2008. Rpn4p is a positive and negative transcriptional regulatior of the ubiquitin-proteasome system. Mol. Biol. 42, 518–525.

    CAS  Google Scholar 

  38. Karpov D.S., Tyutyaeva V.V., Beresten’ S.F., Karpov V.L. 2008. Mapping of the Rpn4p regions responsible for transcriptional activation of proteasome genes. Mol. Biol. 42, 526–532.

    CAS  Google Scholar 

  39. Karpov D.S., Tutyaeva V.V., Karpov V.L. 2008. Mapping of yeast Rpn4p transactivation domains. FEBS Lett. 582, 3459–3464.

    Article  PubMed  Google Scholar 

  40. Zhu Y., Xiao W. 2004. Pdr3 is required for DNA damage induction of MAG1 and DDI1 via a bi-directional promoter element. Nucleic Acids Res. 32, 5066–5075.

    Article  PubMed  CAS  Google Scholar 

  41. Harbison C.T., Gordon D.B., Lee T.I., Rinaldi N.J., Macisaac K.D., Danford T.W., Hannett N.M., Tagne J.B., Reynolds D.B., Yoo J., Jennings E.G., Zeitlinger J., Pokholok D.K., Kellis M., Rolfe P.A., Takusagawa K.T., Lander E.S., Gifford D.K., Fraenkel E., Young R.A. 2004. Transcriptional regulatory code of a eukaryotic genome. Nature. 431, 99–104.

    Article  PubMed  CAS  Google Scholar 

  42. Mannhaupt G., Feldmann H. 2007. Genomic evolution of the proteasome system among hemiascomycetous yeasts. J. Mol. Evol. 65, 529–540.

    Article  PubMed  CAS  Google Scholar 

  43. Gasch A.P., Moses A.M., Chiang D.Y., Fraser H.B., Berardini M., Eisen M.B. 2004. Conservation and evolution of cis-regulatory systems in Ascomycete fungi. PLoS Biol. 2, e398.

    Article  PubMed  Google Scholar 

  44. Lundgren J., Masson P., Realini C.A., Young P. 2003. Use of RNA interference and complementation to study the function of the Drosophila and human 26S proteasome subunit S13. Mol. Cell Biol. 23, 5320–5330.

    Article  PubMed  CAS  Google Scholar 

  45. Meiners S., Heyken D., Weller A., Ludwig A., Stangl K., Kloetzel P.M., Kruger E. 2003. Inhibition of proteasome activity induces concerted expression of proteasome genes and denovo formation of mammalian proteasomes. J. Biol. Chem. 278, 21517–21525.

    Article  PubMed  CAS  Google Scholar 

  46. Chondrogianni N., Tzavelas C., Pemberton A.J., Nezis I.P., Rivett A.J., Gonos E.S. 2005. Overexpression of proteasome beta 5 subunit increases amount of assembled proteasome andconfers ameliorated response to oxidative stress and higher survival rates. J. Biol. Chem. 280, 11840–11850.

    Article  PubMed  CAS  Google Scholar 

  47. Schroder K., Hertzog P.J., Ravasi T., Hume D.A. 2004. Interferon-γ: An overview of signals, mechanisms and functions. J. Leukoc. Biol. 75, 163–189.

    Article  PubMed  CAS  Google Scholar 

  48. Chatterjee-Kishore M., Wright K.L., Ting J.P., Stark G.R. 2000. How Stat1 mediates constitutive gene expression: A complex of unphosphorylated STAT1 and IRF1supports transcription of the LMP2 gene. EMBO J. 19, 4111–4122.

    Article  PubMed  CAS  Google Scholar 

  49. Chondrogianni N., Stratford F.L., Trougakos I.P., Friguet B., Rivett A.J., Gonos E.S. 2003. Central role of the proteasome in senescence and survival of human fibroblasts: Induction of a senescence-like phenotype upon its inhibition and resistance to stress upon its activation. J. Biol. Chem. 278, 28026–28037.

    Article  PubMed  CAS  Google Scholar 

  50. Place R.F., Noonan E.J., Giardia C. 2005. HDACs and the senescent phenotype of WI-38 cells. BMC Cell Biol. 6, 37.

    Article  PubMed  Google Scholar 

  51. Lundgren J., Masson P., Mirzaei Z., Young P. 2005. Identification and characterization of a Drosophila proteasome regulatory network. Mol. Cell. Biol. 25, 4662–4675.

    Article  PubMed  CAS  Google Scholar 

  52. Kwak M.K., Wakabayashi N., Greenlaw J.L., Yamamoto M., Kensler T.W. 2003. Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway. Mol. Cell. Biol. 23, 8786–8794.

    Article  PubMed  CAS  Google Scholar 

  53. Nguyen T., Sherratt P.J., Huang H.C., Yang C.S., Pickett C.B. 2003. Increased protein stability as a mechanism that enhances Nrf2-mediated transcriptional activation of the antioxidant response element. Degradation of Nrf2 by the 26S proteasome. J. Biol. Chem. 278, 4536–4541.

    Article  PubMed  CAS  Google Scholar 

  54. Anderson S.P., Howroyd P., Liu J., Qian X., Bahnemann R., Swanson C., Kwak M.K., Kensler T.W., Corton J.C. 2004. The transcriptional response to a peroxisome proliferators-activated receptor alpha agonist includes increased expression of proteome maintenance genes. J. Biol. Chem. 279, 52390–52398.

    Article  PubMed  CAS  Google Scholar 

  55. Taylor D.M., Kabashi E., Agar J.N., Minotti S., Durham H.D. 2005. Proteasome activity or expression is not altered by activation of the heat shock transcription factor Hsf1 in cultured fibroblasts or myoblasts. Cell Stress Chaperones. 10, 230–241.

    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, 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. O. V. Preobrazhenskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. 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, O.V. Preobrazhenskaya, V.L. Karpov, 2009, published in Molekulyarnaya Biologiya, 2009, Vol. 43, No. 2, pp. 243–252.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karpov, D.S., Preobrazhenskaya, O.V. & Karpov, V.L. Expression regulation of the proteasomal genes in eukaryotes. Mol Biol 43, 223–231 (2009). https://doi.org/10.1134/S0026893309020058

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893309020058

Key words

Search

Navigation