Ukr.Biochem.J. 2022; Volume 94, Issue 5, Sep-Oct, pp. 84-96

doi: https://doi.org/10.15407/ubj94.05.084

Ubiquitin and its role in proteolisis: the 2004 Nobel prize in chemistry

O. P. Matyshevska*, M. V. Grigorieva,
V. M. Danilova, S. V. Komisarenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: matysh@yahoo.com

Received: 11 November 2021; Revised: 29 September 2022;
Accepted: 04 November 2022; Available on-line: 19 December 2022

In the early 1980-s, Aaron Ciechanover, Avram Hershko, and Irwin Rose discovered one of the most important cyclic cellular processes – a regulated ATP-dependent protein degradation, for which they were awarded the 2004 Nobel Prize in Chemistry. These scientists proved the existence of a non-lysosomal proteolysis pathway and completely changed the perception of intracellular protein degradation mechanisms. They demonstrated pre-labelling of a doomed protein in a cell with a biochemical marker called ubiquitin. Polyubiquitylation of a protein as a signal for its proteolysis was a new mechanism discovered as a result of collaborative efforts of three scientists on isolation of enzymes involved in this sequential process, clarification of the biochemical stages, and substantiating the energy dependence mechanism. The article contains biographical data of the Nobel laureates, the methods applied, and the history of the research resulted in the discovery of the phenomenon of proteasomal degradation of ubiquitin-mediated proteins.

Keywords: , , , , ,


References:

  1. Avram Hershko – Biographical. Regime of access : https://www.nobelprize.org/prizes/chemistry/2004/hershko/biographical/
  2. Hershko A, Tomkins GM. Studies on the degradation of tyrosine aminotransferase in hepatoma cells in culture. Influence of the composition of the medium and adenosine triphosphate dependence. J Biol Chem. 1971;246(3):710-714. PubMed
  3. Etlinger JD, Goldberg AL. A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes. Proc Natl Acad Sci USA. 1977;74(1):54-58. PubMed, PubMedCentral, CrossRef
  4. Sudakin V, Ganoth D, Dahan A, Heller H, Hershko J, Luca FC, Ruderman JV, Hershko A. The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol Biol Cell. 1995;6(2):185-197. PubMed, PubMedCentral, CrossRef
  5. Rose IA, Schweigert BS. Effect of vitamin B12 on nucleic acid metabolism of the rat. Proc Soc Exp Biol Med. 1952;79(3):541-544. PubMed, CrossRef
  6. Rose IA, Schweigert BS. Incorporation of C14 totally labeled nucleosides into nucleic acids. J Biol Chem. 1953;202(2):635-645. PubMed
  7. Haas AL, Murphy KE, Bright PM. The inactivation of ubiquitin accounts for the inability to demonstrate ATP, ubiquitin-dependent proteolysis in liver extracts. J Biol Chem. 1985;260(8):4694-4703. PubMed
  8. Rose IA, O’Connell EL, Litwin S. Determination of the rate of hexokinase-glucose dissociation by the isotope-trapping method. J Biol Chem. 1974;249(16):5163-5168. PubMed
  9. Ciehanover A, Hod Y, Hershko A. A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem Biophys Res Commun. 1978;81(4):1100-1105. PubMed, CrossRef
  10. Aaron Ciechanover. Regime of access : https://uk.wikipedia.org/wiki/
  11. Ciechanover A, Heller H, Elias S, Haas AL, Hershko A. ATP-dependent conjugation of reticulocyte proteins with the polypeptide required for protein degradation. Proc Natl Acad Sci USA. 1980;77(3):1365-1368. PubMed, PubMedCentral, CrossRef
  12. Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA. Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc Natl Acad Sci USA. 1980;77(4):1783-1786. PubMed, PubMedCentral, CrossRef
  13. Goldknopf IL, Busch H. Isopeptide linkage between nonhistone and histone 2A polypeptides of chromosomal conjugate-protein A24. Proc Natl Acad Sci USA. 1977;74(3):864-868. PubMed, PubMedCentral, CrossRef
  14. Ciechanover A, Elias S, Heller H, Ferber S, Hershko A. Characterization of the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulocytes. J Biol Chem. 1980;255(16):7525-7528. PubMed
  15. Wilkinson KD, Urban MK, Haas AL. Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. J Biol Chem. 1980;255(16):7529-7532. PubMed
  16. Goldstein G. Isolation of bovine thymin: a polypeptide hormone of the thymus. Nature. 1974;247(5435):11-14. PubMed, CrossRef
  17. Popular information. Regime of access : https://www.nobelprize.org/prizes/chemistry/2004/popular-information/
  18. Ciechanover A, Elias S, Heller H, Hershko A. “Covalent affinity” purification of ubiquitin-activating enzyme. J Biol Chem. 1982;257(5):2537-2542. PubMed
  19. Hershko A, Heller H, Elias S, Ciechanover A. Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem. 1983;258(13):8206-8214. PubMed
  20. Ciechanover A. The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J. 1998;17(24):7151-7160. PubMed, PubMedCentral, CrossRef
  21. Haas AL, Rose IA. The mechanism of ubiquitin activating enzyme. A kinetic and equilibrium analysis. J Biol Chem. 1982;257(17):10329-10337. PubMed
  22. Hershko A, Heller H, Eytan E, Reiss Y. The protein substrate binding site of the ubiquitin-protein ligase system. J Biol Chem. 1986;261(26):11992-11999. PubMed
  23. Hershko A, Leshinsky E, Ganoth D, Heller H. ATP-dependent degradation of ubiquitin-protein conjugates. Proc Natl Acad Sci USA. 1984;81(6):1619-1623. PubMed, PubMedCentral, CrossRef
  24. Waxman L, Fagan JM, Goldberg AL. Demonstration of two distinct high molecular weight proteases in rabbit reticulocytes, one of which degrades ubiquitin conjugates. J Biol Chem. 1987;262(6):2451-2457. PubMed
  25. Hoffman L, Pratt G, Rechsteiner M. Multiple forms of the 20 S multicatalytic and the 26 S ubiquitin/ATP-dependent proteases from rabbit reticulocyte lysate. J Biol Chem. 1992;267(31):22362-22368. PubMed
  26. Regime of access : https://www.caltagmedsystems.co.uk/
  27. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82(2):373-428. PubMed, CrossRef
  28. Sakamoto KM. Ubiquitin-dependent proteolysis: its role in human diseases and the design of therapeutic strategies. Mol Genet Metab. 2002;77(1-2):44-56. PubMed, CrossRef
  29. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H. Identification of a primary target of thalidomide teratogenicity. Science. 2010;327(5971):1345-1350. PubMed, CrossRef
  30. Stewart AK. Medicine. How thalidomide works against cancer. Science. 2014;343(6168):256-257. PubMed, PubMedCentral, CrossRef
  31. Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ. Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proc Natl Acad Sci USA. 2001;98(15):8554-8559. PubMed, PubMedCentral, CrossRef
  32. Guedeney N, Cornu M, Schwalen F, Kieffer C, Voisin-Chiret AS. PROTAC technology: A new drug design for chemical biology with many challenges in drug discovery. Drug Discov Today. 2022;28(1):103395. PubMed, CrossRef

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