The Nobel Prize in Chemistry 2004

Press Release: The Nobel Prize in Chemistry 2004 6 October 2004 The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2004 "for the discovery of ubiquitin-mediated protein degradation" jointly to   Proteins labelled for destruction Proteins build up all living things: plants, animals and therefore us humans. In the past few decades biochemistry has come a long way towards explaining how the cell produces all its various proteins. But as to the breaking down of proteins, not so many researchers were interested. Aaron Ciechanover, Avram Hershko and Irwin Rose went against the stream and at the beginning of the 1980s discovered one of the cell's most important cyclical processes, regulated protein degradation. For this, they are being rewarded with this year's Nobel Prize in Chemistry. Aaron Ciechanover, Avram Hershko and Irwin Rose have brought us to realise that the cell functions as a highly-efficient checking station where proteins are built up and broken down at a furious rate. The degradation is not indiscriminate but takes place through a process that is controlled in detail so that the proteins to be broken down at any given moment are given a molecular label, a ‘kiss of death', to be dramatic. The labelled proteins are then fed into the cells' "waste disposers", the so called proteasomes, where they are chopped into small pieces and destroyed. The label consists of a molecule called ubiquitin. This fastens to the protein to be destroyed, accompanies it to the proteasome where it is recognised as the key in a lock, and signals that a protein is on the way for disassembly. Shortly before the protein is squeezed into the proteasome, its ubiquitin label is disconnected for re-use. Thanks to the work of the three Laureates it is now possible to understand at molecular level how the cell controls a number of central processes by breaking down certain proteins and not others. Examples of processes governed by ubiquitin-mediated protein degradation are cell division, DNA repair, quality control of newly-produced proteins, and important parts of the immune defence. When the degradation does not work correctly, we fall ill. Cervical cancer and cystic fibrosis are two examples. Knowledge of ubiquitin-mediated protein degradation offers an opportunity to develop drugs against these diseases and others. Read more about this year's prize Information for the Public Advanced Information (pdf) Links and Further Reading   Aaron Ciechanover Aaron Ciechanover, born 1947 (57 years) in Haifa, Israel (Israeli citizen). Doctor's degree in medicine in 1981 at the Technion (Israel Institute of Technology), Haifa. Professor at the Unit of Biochemistry and Director of the Rappaport Family Institute for Research in Medical Sciences at the Technion, Haifa, Israel. 2004 Publication: Ciechanover A. The ubiquitin proteolytic system and pathogenesis of human diseases: a novel platform for mechanism-based drug targeting., Biochem Soc Trans. 2004 Oct 08;132(3):103-107 Nadav E, Shmueli A, Barr H, Gonen H, Ciechanover A, Reiss Y. A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1., Biochem Biophys Res Commun. 2004 Oct 08;132(3):103-107 Lingbeck JM, Trausch-Azar JS, Ciechanover A, Schwartz AL. Determinants of nuclear and cytoplasmic ubiquitin-mediated degradation of MyoD., J Biol Chem. 2004 Oct 08;132(3):103-107 Herrmann J, Edwards WD, Holmes DR Jr, Shogren KL, Lerman LO, Ciechanover A, Lerman A. Increased ubiquitin immunoreactivity in unstable atherosclerotic plaques associated with acute coronary syndromes., J Am Coll Cardiol. 2004 Oct 08;132(3):103-107 Ryoo HD, Bergmann A, Gonen H, Ciechanover A, Steller H. Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1., Nat Cell Biol. 2004 Oct 08;132(3):103-107 Amir RE, Iwai K, Ciechanover A. The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105., J Biol Chem. 2004 Oct 08;132(3):103-107 Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction., Physiol Rev. 2004 Oct 08;132(3):103-107   Avram Hershko Avram Hershko, (Avram Hershko's page at Technion (Israel Institute of Technology) born 1937 (67 years) in Karcag, Hungary (Israeli citizen). Doctor's degree in medicine in 1969 at the Hadassah Medical School of the Hebrew University, Jerusalem. Distinguished Professor at the Rappaport Family Institute for Research in Medical Sciences at the Technion (Israel Institute of Technology), Haifa, Israel.   Representative Publications Sudakin V., Ganoth D., Dahan A., Heller H., Hershko J., Luca F.C., Ruderman J.V. and Hershko A. (1995). The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol. Biol. Cell; 6, 185-198. Carrano A., Eytan E., Hershko A. and Pagano M. (1999). SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nature Cell Biol.; 1, 193-199. Ganoth D., Bornstein G., Ko T. K., Larsen B., Tyers M., Pagano M. and Hershko A. (2001). The cell cycle regulatory protein Cks1 is required for the SCFSkp2-mediated ubiquitinylation of p27. Nature Cell Biol.; 3, 321-324. 2004 Publication: Hershko AY, Ulmansky R, Moallem E, Naparstek Y. Susceptibility and resistance to experimental adjuvant arthritis. Front Biosci. 2004 Sep 01;9:3268-75. Shlomai A, Hershko AY, Gabbay E, Ben-Chetrit E. Clinical and radiographic features mimicking pulmonary embolism as the first manifestation of Takayasu's arteritis. Clin Rheumatol. 2004 Oct;23(5):470-2. Epub 2004 Jul 02. Abuksis G, Orenstein S, Hershko A, Michowiz R, Livne M, Loia N, Kremer I, Winbereger D. Cornea recipients: are their opinions and attitudes toward organ donation different from those of the general population? Transplant Proc. 2004 Jun;36(5):1249-52. Moshe Y, Boulaire J, Pagano M, Hershko A. Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, aregulator of the anaphase promoting complex/cyclosome. Proc Natl Acad Sci U S A. 2004 May 25;101(21):7937-42. Epub 2004 May 17. Donzelli M, Busino L, Chiesa M, Ganoth D, Hershko A, Draetta GF. Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. Cell Cycle. 2004 Apr;3(4):469-71. Epub 2004 Apr 01. Elinav H, Israeli E, Shibolet O, Hershko A, Sela C, Migdal A, Ilan Y. Idiopathic liver involvement in Turner syndrome. Isr Med Assoc J. 2004 Jan;6(1):56-7. Review. No abstract available.   Irwin Rose Irwin Rose, born 1926 (78 years) in New York, USA (American citizen). Doctor's degree in 1952 at the University of Chicago, USA. Specialist at the Department of Physiology and Biophysics, College of Medicine, University of California, Irvine, USA.