Molecular Biology Reports

, Volume 26, Issue 1–2, pp 125–130 | Cite as

Endoplasmic reticulum degradation. Reverse protein transport and its end in the proteasome

  • Richard K. Plemper
  • Dieter H. Wolf
Article

Abstract

Degradation of misfolded or unassembled proteins of the secretory pathway is an essential function of the quality control system of the Endoplasmic Reticulum (ER). Using yeast as a model organism we show that a mutated and therefore misfolded soluble lumenal protein carboxypeptidase yscY (CPY*), and a polytopic membrane protein, the ATP-binding cassette transporter Pdr5 (Pdr5*), are retrograde transported out of the ER and degraded via the cytoplasmic ubiquitin-proteasome system. Retrograde transport depends on an intact Sec61 translocon. Complete import of CPY* into the lumen of the ER requests a new targeting mechanism for retrograde transport of the malfolded enzyme through the Sec61 channel to occur. For soluble CPY*, but not for the polytopic membrane protein Pdr5* action of the ER-lumenal Hsp70 chaperone Kar2 is necessary to deliver the protein to the ubiquitin-proteasome machinery. Polyubiquitination of CPY* and Pdr5* by the ubiquitin conjugating enzymes Ubc6 and Ubc7 is crucial for degradation to occur. Also transport of CPY* out of the ER-lumen depends on ubiquitination. Newly discovered proteins of the ER membrane, Der1, Der3/Hrd1, and Hrd3 are specifically involved in the retrograde transport processes.

endoplasmic reticulum ER associated degradation proteasome yeast Saccharomyces cerevisiae 

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References

  1. 1.
    Rapoport TA, Jungnickel B & Kutay U (1996) Annu. Rev. Biochem. 65: 271–303Google Scholar
  2. 2.
    Gaut JR & Hendershot LM (1993) Curr. Opin. Cell Biol. 5: 589–595Google Scholar
  3. 3.
    Klausner RD & Sitia R (1990) Cell 62: 611–614Google Scholar
  4. 4.
    Bonifacino JS & Klausner RD (1994). In: Ciechanover AE & Schwartz AL (Eds) Modern Cell Biology, Cellular Proteolysis Systems (Vol. 15, pp. 137–160) Wiley-Liss., New YorkGoogle Scholar
  5. 5.
    Hieter P, Bassett Jr, DE & Valle D (1996) Nature Genet. 13: 253–255Google Scholar
  6. 6.
    Kopito RR (1997) Cell 88: 427–430Google Scholar
  7. 7.
    Sommer T & Wolf DH (1997) FASEB J. 11: 1227–1233Google Scholar
  8. 8.
    Wolf DH & Fink GR (1975) J. Bacteriol. 123: 1150–1156Google Scholar
  9. 9.
    Finger A, Knop M & Wolf DH (1993) Eur. J. Biochem. 218: 565–574Google Scholar
  10. 10.
    Egner R, Rosenthal FE, Kralli A, Sanglard D & Kuchler K (1998) Mol. Biol. Cell 9: 523–543Google Scholar
  11. 11.
    Hiller MM, Finger A, Schweiger M & Wolf DH (1996) Science 273: 1725–1728Google Scholar
  12. 12.
    Biederer T, Volkwein C & Sommer T (1997) Science 278: 1806–1809Google Scholar
  13. 13.
    Bordallo J, Plemper RK, Finger A & Wolf DH (1998) Mol. Biol. Cell 9: 209–222Google Scholar
  14. 14.
    Blobel G (1995) Cold Spring Harbor Symp. Quant. Biol. 60: 1–10Google Scholar
  15. 15.
    Plemper RK, Böhmler S, Bordallo J, Sommer T & Wolf DH (1997) Nature 388: 891–895Google Scholar
  16. 16.
    Dürr G, Strayle J, Plemper R, Elbs S, Klee S, Catty P, Wolf DH & Rudolph HK (1998) Mol. Biol. Cell 9: 1149–1162Google Scholar
  17. 17.
    Plemper RK, Deak PM, Otto RT & Wolf DH (1999) FEBS Lett. 443: 241–245Google Scholar
  18. 18.
    Knop M, Finger A, Braun T, Hellmuth K & Wolf DH (1996) EMBO J. 15: 753–763Google Scholar
  19. 19.
    Hampton RY, Gardner RG & Rine J (1996) Mol. Biol. Cell 7: 2029–2044Google Scholar
  20. 20.
    Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL & Riordan JR (1995) Cell 83: 129–135Google Scholar
  21. 21.
    Ward CL, Omura S & Kopito RR (1995) Cell 83: 121–127Google Scholar
  22. 22.
    Egner R, Mahé Y, Pandjaitan R & Kuchler K (1995) Mol. Cell Biol. 15: 5879–5887Google Scholar
  23. 23.
    Plemper RK, Egner R, Kuchler K & Wolf DH (1998) J. Biol. Chem. 273: 32848–32856Google Scholar
  24. 24.
    Hamman BD, Hendershot LM & Johnson AE (1998) Cell 92: 747–758Google Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Richard K. Plemper
    • 1
  • Dieter H. Wolf
    • 1
  1. 1.Institut für BiochemieUniversität StuttgartStuttgartGermany

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