CURRICULUM VITAE of 2004 NOBEL PRIZE IN CHEMISTRY LAUREATE

DISTINGUISHED PROFESSOR AVRAM HERSHKO

 

July 2004

Name:    Hershko, Avram.

 

Date of Birth: December 31,1937.

 

Place of Birth: Karcag, Hungary.

 

Immigrated to Israel: 1950.

 

Marital status: Married, three children.

 

Address :       Unit of Biochemistry, The B. Rappaport Faculty of Medicine

Technion-Israel Institute of Technology

P.O.Box 9649, Haifa 31096, Israel.

Telephone:       9724-8295344

Fax:                  9724-8535773

 

Education:

 

1965  M. D.       The Hebrew University-Hadassah Medical School,

                             Jerusalem, Israel. ( Cum Laude ).

 

1969  Ph. D.      The Hebrew University-Hadassah Medical School,

                             Jerusalem, Israel. ( Summa Cum Laude ).

 

Employment and Professional Experience.

 

1965-1967         Physician, Israel Defense Forces                       

 

1967-1969         Lecturer, Department of Biochemistry, The Hebrew

                          University- Hadassah Medical School, Jerusalem, Israel.

 

1969-1971         U.S.P.H.S. International Postdoctoral Fellowship, Dept. of

                            Biochemistry and Biophysics, University of California

                          Medical Center, San Francisco, CA, USA.  .

 

1972-1980         Associate Professor, Unit of Biochemistry, Faculty of Medicine,

                           Technion-Israel Institute of Technology, Haifa Israel.

 

1980-1998          Professor, Unit of Biochemistry, Faculty of Medicine,

                          Technion-Israel Institute of Technology, Haifa, Israel.

 

1998-present     Distinguished  Professor, Technion-Israel Institute of Technology

 

 

Awards and Honors.

 

1987                                      The Weizmann Prize for Sciences, Tel Aviv, Israel.

 

1993                                        Member, European Molecular Biology Organization ( EMBO ).

 

1994                                        The Israel Prize in Biochemistry, Jerusalem, Israel.

 

1999                                      The Gairdner Foundation International Award, Toronto, Canada (with A. Varshavsky).

 

þ1999                  The Wachter Foundation Award, Innsbruck, Austria (with A.          Ciechanover).

 

2000                                      The Alfred P. Sloan Prize of the General Motors Cancer Research Foundation (with A. Varshavsky).

 

2000               Member, Israel Academy of Sciences            

 

2000              Albert Lasker Basic Medical Research Award (with A.               

                      Ciechanover and A. Varshavsky).

 

2001                                      The American Society for Biochemistry and Molecular Biology-

                       Merck Award  (with A. Varshavsky).

 

2001               The Wolf Prize for Medicine, Jerusalem, Israel (with A.   

                  Varshavsky). 

 

2001               The  Massry Prize (with A. Varshavsky)

 

2001               The Louisa Gross Horwitz Prize (with A. Varshavsky)

 

2002                                      The Emet Prize for Medicine, Israel (with A. Ciechanover).

 

2002                         The E. B. Wilson Medal of The American Society of Cell Biology  (with A. Varshavsky).

 

2003                   Foreign Associate,  US National Academy of Sciences

 

 

 

 

                       

 

 

Publications.

 

A. Original Papers.

 

1.         Hershko, A., Amoz, S. and Mager, J. (1961) Effect of polyamines and bivalent metals on in vitro  incorporation of amino acids into ribonucleoprotein particles. Biochem. Biophys. Res. Commun. 5, 46-51.

 

2.         Hershko, A., Wind, E., Razin, A. and Mager,J. (1963) Conversion of guanine to hypoxanthine in mammalian red blood cells. Biochim. Biophys. Acta  71, 609-620.

 

3.         Mager, J., Razin, A., Hershko, A. and Izak, G. (1964) The mechanism of red cell hexokinase inhibition induced by oxidation of intracellular glutathione and its relation to drug sensitivity. Biochem. Biophys. Res. Commun. 17 ,703-708.

 

4.         Hershko, A. and Kindler, S. H. (1966) Mode of interaction of purine nucleotides and amino acids with glutamate dehydrogenase. Biochem. J.101, 661-664.

 

5.         Mager, J., Hershko, A., Zeitlin-Beck, R., Shoshani, T. and Razin, A. (1967) Turnover of purine nucleotides in rabbit erythrocytes. I. Studies in vivo. Biochim. Biophys. Acta 149, 50-58.

 

6.         Hershko, A., Razin, A., Shoshani, T. and Mager, J. (1967) Turnover of purine nucleotides in rabbit erythrocytes. II. Studies in vitro. Biochim. Biophys. Acta 149, 59-73.

 

7.         Razin, A., Hershko, A., Glaser, G. and Mager, J.(1968) The oxidant effect of isouramyl on red cell glutathione and its synergistic enhancement by ascorbic acid or 2,4-dihydroxyphenylalanine. Israel J. Med. Sci. 4, 852-857.

 

8.         Hershko, A., Hershko, C. and Mager, J. (1968) Increased formation of 5-phosphoribosyl-1-pyrophosphate in red blood cells of some gouty patients. Israel J. Med. Sci. 4, 939-944.

 

9.         Hershko, A,. Jabotinsky, C. and Mager, J. (1969) Studies on red cell nucleoside triphosphate pyrophosphohydrolase. Israel J. Med. Sci. 5, 997.

 

10.      Hershko, A., Razin, A. and Mager, J. (1969) Regulation of the synthesis of 5-phosphoribosyl-1-pyrophosphate in intact red blood cells and in cell-free preparations. Biochim. Biophys. Acta 184, 64-76.

 

11.      Hershko, A. and Tomkins, G.M. (1971) 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.  246, 710-714.

 

12.      Hershko, A., Mamont, P., Shields, R. and Tomkins, G. M. (1971) Pleiotypic response. Nature ( New Biology ) 232, 206-211.

 

13.      Mamont, P., Hershko, A., Kram, R., Schacter, L., Lust, J. and Tomkins, G. M. (1972) The pleiotypic response in mammalian cells : Search for an intracellular mediator. Biochem. Biophys. Res. Commun. 48, 1378-1384.

 

14.      Shechter, Y., Rafaeli-Eshkol, D. and Hershko, A. (1973) Influence of protease inhibitors and energy metabolism on intracellular protein breakdown in starving E.coli.

Biochem. Biophys. Res. Commun. 54, 1518-1524.

 

15.      Morhenn, V., Kram, R., Hershko, A. and Tomkins, G. M. (1974) Studies on amino acid control of cellular function. Cell 1, 91-94.

 

16.      Rafaeli-Eshkol, D. and Hershko, A. (1974) Regulation of intracellular protein breakdown in stringent and relaxed strains of E. coli.  Cell 2, 31-35.

 

17.      Rafaeli-Eshkol, D., Epstein, D. and Hershko, A. (1974) Roles of protein synthesis and tRNA aminoacylation in the regulation of intracellular protein breakdown in E. coli. Biochem. Biophys. Res. Commun. 61, 899-905.

 

18.      Aviram, M. and Hershko, A. (1975) Influence of ATP depletion on the degradation of rapidly labelled RNA in cultured hepatoma cells. Biochem. Biophys. Commun. 65, 1313.

 

19.      Epstein, D., Elias-Bishko, S. and Hershko, A. (1975) Requirement for protein synthesis in the regulation of protein breakdown in cultured hepatoma cells. Biochemistry 14, 5199-5204.

 

20.      Hod, .Y. and Hershko, A. (1976) Relationship of the pool of intracellular valine to protein synthesis and degradation in cultured cells. J. Biol. Chem. 251, 4458-4467.

 

21.      Ciechanover, A. and Hershko, A. (1976) Early effects of serum on phospholipid metabolism in untransformed and oncogenic virus-transformed fibroblasts. Biochem. Biophys. Res. Commun. 73, 85.

 

22.      Aviram, M. and Hershko, A. (1977) Interconversion of multiple forms of tyrosine aminotransferase in vitro  and in vivo  in cultured hepatoma cells. Biochim. Biophys. Acta 498, 83-90.

 

23.      Kaftori, A., Hershko, A. and Fry, M. (1978) Protein turnover in senescent chick embryo fibroblasts. J. Cell. Physiol. 94, 147-160.

 

24.      Ciechanover, A., Hod, Y. and Hershko, A. (1978). A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem. Biophys. Res. Commun. 81, 1100-1105.

 

25.      Hershko, A., Ciechanover, A. and Rose, A. (1979). Resolution of an ATP-dependent proteolytic system from reticulocytes : a component that interacts with ATP. Proc Natl. Acad. Sci. USA. 76, 3107-3110.

 

26.      Rose, I. A., Warms, J. V. B. and Hershko, A. (1979) A high molecular weight protease in liver cytosol. J. Biol. Chem. 254, 8135-8138.

 

27.      Ciechanover, A., Heller, H., Elias, S., and Hershko, A. (1980) ATP-dependent conjugation of reticulocyte proteins with the polypeptide required for protein degradation. Proc Natl. Acad. Sci. USA.77, 1365-1368.

 

28.      Hershko, A., Ciechanover, A., Heller, H., Haas, A. l. and Rose, I. A. (1980). Proposed role of ATP in protein breakdown : conjugation of proteins with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc.Natl. Acad. Sci. USA 77, 1783-1786.

 

29.      Ciechanover, A., Elias, S., Heller, H., Ferber, S. and Hershko, A. (1980) Characterization of the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulocytes. J. Biol. Chem. 255, 7525-7528.

 

30.      Ciechanover, A., Heller, A., Katz-Etzion, R. and Hershko, A. (1981) Activation of the heat-stable polypeptide of the ATP-dependent proteolytic system. Proc. Natl. Acad. Sci. USA 78, 761-765.

 

31.      Hershko, A., Ciechanover, A. and Rose, I.A. (1981). Identification of the active amino acid residue of the polypeptide of ATP-dependent protein breakdown. J. Biol. Chem. 256, 1525-1528.

 

32.      Ciechanover, A., Elias, S., Heller, H. and Hershko, A. (1982). " Covalent affinity" purification of ubiquitin-activating enzyme. J.Biol. Chem.  257, 2537-2542.

 

33.      Haas, A. L., Warms, J. V. B., Hershko, A. and Rose, I. A. (1982) Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin ligation. J. Biol. Chem. 257, 2543-2548.

 

34.      Hershko, A., Eytan, E. and Ciechanover, A. ( 1982). Immunochemical analysis of the turnover of ubiquitin-protein conjugates in intact cells. J. Biol. Chem. 257, 13964-13970.

 

35.      Hershko, A., Heller, H., Elias, S. and Ciechanover, A. (1983). Components of ubiquitin-protein ligase system : resolution, affinity purification and role in protein breakdown. J. Biol. Chem. 258, 8206-8214.

 

36.      Hershko, A., Leshinsky, E. Ganoth, D. and Heller, H. (1984). ATP-dependent degradation of ubiquitin-protein conjugates. Proc. Natl. Acad. Sci. USA. 81, 1619-1623.

 

37.      Eytan, E. and Hershko, A. (1984) Relevance of protease "inhibitor" to the ATP-ubiquitin proteolytic system. Biochem. Biophys. Res. Commun. 122, 116-123.

 

38.      Hershko, A., Heller, H., Eytan, E., Kaklij, G. and Rose, I. A. (1984) Role of                  a-amino group of protein in ubiquitin-mediated protein breakdown. Proc. Natl. Acad. Sci. USA 81, 7021-7025.

 

39.      Hershko, A. and Heller, H. (1985). Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem. Biophys. Res. Commun. 128, 1079-1086.

 

40.      Hershko, A., Heller, H., Eytan, E. and Reiss, Y. (1986). The protein substrate binding site of the ubiquitin-protein ligase system. J. Biol. Chem. 261, 11992-11999.

 

41.      Hershko, A. and Rose, I.A. (1987). Ubiquitin-aldehyde : a general inhibitor of ubiquitin-recycling processes.  Proc. Natl. Acad. Sci. USA. 84, 1829-1833.

 

42.      Raviv, O., Heller, H. and Hershko, A. (1987) Alterations in components of the ubiquitin-protein ligase system following maturation of reticulocytes to erythrocytes. Biochem. Biophys. Res. Commun. 145, 658-665.

 

43.      Reiss, Y., Kaim, D. and Hershko, A. (1988). Specificity of binding of NH2-terminal residue of proteins to ubiquitin-protein ligase. Use of amino acid derivatives to characterize specific binding sites. J. Biol. Chem. 263, 2693-2698.

 

44.      Ciechanover, A., Ferber, S., Ganoth, D., Elias, S., Hershko, A. and Arfin, S. (1988) Purification and characterization of arginyl-tRNA protein transferase from rabbit reticulocytes : Its involvement in post-translational modification and degradation of acidic NH2-termini substrates of the ubiquitin pathway. J. Biol. Chem. 263, 11155-11167.

 

45.      Ganoth, D., Leshinsky, E., Eytan, E. and Hershko, A. (1988). A multicomponent system that degrades proteins conjugated to ubiquitin. Resolution of components and evidence for ATP-dependent complex formation. J. Biol. Chem. 263, 12412-12419.

 

46.      Reiss, Y., Heller, H. and Hershko, A. (1989) Binding sites of ubiquitin-protein ligase. Binding of ubiquitin-protein conjugates and of ubiquitin-carrier protein. J. Biol. Chem. 264,10378-10383.

 

47.      Eytan, E., Ganoth, D., Armon, T. and Hershko, A. (1989). ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin. Proc. Natl. Acad. Sci. USA. 86, 7751-7755.

 

48.      Reiss, Y. and Hershko, A. (1990). Affinity purification of ubiquitin-protein ligase on immobilized protein substrates. Evidence for the existence of separate NH2-terminal binding sites on a single enzyme. J. Biol Chem. 265, 3685-3690.

 

49.      Heller, H. and Hershko, A. (1990) A ubiquitin-protein ligase specific for type III protein substrates. J. Biol. Chem. 265, 6532-6535.

 

50.      Armon, T., Ganoth, D. and Hershko, A. (1990) Assembly of the 26S complex that degrades proteins ligated to ubiquitin is accompanied by the formation of ATPase activity. J. Biol. Chem. 265, 20723-20726.

 

51.      Hershko, A., Ganoth, D., Pehrson, J. Palazzo, R.E. and Cohen, L.H. (1991). Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. J. Biol. Chem. 266, 16376-16379.

 

52.      Hadari, T. Warms, J.W.B., Rose, I.A. and Hershko, A. (1992). A ubiquitin-C-terminal isopeptidase that acts on polyubiquitin chains. Role in protein degradation. J. Biol. Chem. 267, 719-727.

 

53.      Eytan, E., Armon, T., Heller, H., Beck, S. and Hershko, A. (1993). Ubiquitin-C-terminal hydrolase activity associated with the 26S protease complex. J. Biol. Chem. 268, 4668-4674.

 

54.      Hershko, A., Ganoth, D., Sudakin, V., Dahan, A., Cohen, L.H., Luca, F.C., Ruderman, J.V. and Eytan, E. (1994). Components of a system that ligates cyclin to ubiquitin and their regulation by protein kinase cdc2. J. Biol. Chem. 269, 4940-4946.

 

55.      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.

 

56.      Lahav-Baratz S., Sudakin, V., Ruderman, J.V  and Hershko, A. (1995). Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase. Proc. Natl. Acad. Sci. USA 92, 9303-9307.

 

57.      Aristarkhov, A., Eytan, E., Moghe, A., Admon, A., Hershko, A. and Ruderman, J.V. (1996). E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins. Proc. Natl.Acad. Sci. USA ,93, 4294-4299.

 

58.      Townsley, F.M., Aristarkhov, A., Beck, S., Hershko, A. and Ruderman, J.V. (1997). Dominant-negative cyclin-selective ubiquitin-carrier protein E2-C/UbcH10 blocks cells in metaphase. Proc. Natl. Acad. Sci. USA 94, 2362-2367.

 

59.      Sudakin, V., Shteinberg, M., Ganoth, D., Hershko, J. and Hershko, A. (1997). Binding of activated cyclosome to p13suc1. Use for affinity purification. J. Biol. Chem. 272, 18051-18059.

 

60.      Shteinberg, M. and Hershko, A. (1999). Role of Suc1 in the activation of the cyclosome by protein kinase Cdk1/cyclin B.  Biochem. Biophys. Res. Commun. 257, 12-18.

 

61.      Montagnoli, A., Fiore, F., Eytan, E., Carrano, A. C., Draetta, G. F., Hershko, A. and Pagano, M. (1999). Ubiquitination of p27 is regulated by Cdk-dependent phosphorylation and trimeric complex formation. Genes & Dev. 13, 1181-1189.

 

62.      Shteinberg, M., Protopopov, Y., Listovsky, T., Brandeis, M. and Hershko, A. (1999).  Phosphorylation of the cyclosome is required for its stimulation by Fizzy/Cdc20. Biochem. Biophys. Res. Commun. 260, 193-198.

 

63.      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.

 

64. Yudkovsky, Y., Shteinberg, M., Listovsky, T. Brandeis, M. and Hershko, A. (2000) Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint. Biochem. Biophys. Res. Commun. 271, 299-304.

 

65.  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.

 

66.             Hershko, D., Bornstein, G., Ben-Izhak, O., Carrano, A., Pagano, M., Krausz, M. M. and Hershko, A. (2001). Inverse relationship between levels of p27Kip1 and of its ubiquitin ligase subunit Skp2 in colorectal cancers. Cancer  91, 1745-1751.

 

67.             Golan, A., Yudkovsky, Y. and  Hershko, A. (2002). The cyclin-ubiquitin ligase activity of the cyclosome/APC is jointly activated by protein kinases Cdk1/cyclin B and Plk. J. Biol. Chem. 277, 15552-15557.

 

68.      Donzelli, M., Squatrito, M., Ganoth, D., Hershko, A., Pagano, M.  and Draetta, G. (2002). Dual mode of degradation of Cdc25A phosphatase. EMBO J. 21, 4876-4884.

 

69.             Sitry, D., Seeliger, M., Ko, T. K., Ganoth, D., Breward, S. E., Itzhaki, L. S., Pagano, M. and Hershko, A. (2002). Three different binding sites of Cks1 are required for p27-ubiquitin ligation. J. Biol. Chem. 277, 42233-42240.

 

70.       Busino, L., Donzelli, M., Chiesa, M., Guardavaccaro, D., Ganoth, D., Dorrello, N. V., Hershko, A., Pagano, M. and Draetta, G. (2003). Degradation of Cdc25A by bTrCP during S-phase and in response to DNA damage. Nature 426, 87-91.

 

 

71.             Bornstein, G., Bloom, J., Sitry-Shevah, D., Nakayama, K., Pagano, M. and Hershko, A. (2003) Role of SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S-phase. J. Biol. Chem. 278, 25752-25757.

 

72.      Moshe, Y., Boulaire, J., Pagano, M. and Hershko, A. (2004) Role of Polo- like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase-promoting complex/cyclosome. Proc. Natl. Acad. Sci. USA, 101, 7937-7942.

 

 

 

 

 

B.  Review Articles.

 

1.         Hershko, A. and Fry, M. (1975) Post-translational cleavage of polypeptide chains: Role in assembly. Annu. Rev. Biochem. 44, 775-797.

 

2.         Hershko, A. and Ciechanover, A. (1982) Mechanisms of intracellular protein breakdown. Annu. Rev. Biochem. 51, 335-364.

 

3.         Hershko, A. (1983) Ubiquitin: roles in protein modification and breakdown. Cell 34, 11-12.

 

4.         Hershko, A. and Ciechanover, A. (1986) The ubiquitin pathway for the degradation of intracellular proteins. Progr. Nucl. Ac. Res. Mol. Biol. 33, 19-56.

 

5.         Hershko, A. (1988). Ubiquitin-mediated protein degradation. J. Biol. Chem. 263, 15237-15240. (Minireview).

 

6.         Hershko, A. (1991) The ubiquitin pathway for protein degradation. Trends Biochem. Sci. 16, 265-268.

 

7.         Hershko, A. and Ciechanover, A. (1992). The ubiquitin system for protein degradation. Annu Rev. Biochem. 61, 761-807.

 

8.                 Hershko, A. (1996). Lessons from the discovery of the ubiquitin system. Trends Biochem. Sci., 21, 445-449.

 

9.                 Hershko, A. (1997). Roles of ubiquitin-mediated proteolysis in cell cycle control. Curr. Op. Cell Biol. 9, 788-799.

 

10.             Hershko, A. and Ciechanover, A. (1998). The ubiquitin system. Annu. Rev. Biochem. 67, 425-479.

 

11.             Hershko, A. (1999). Mechanisms and regulation of the degradation of cyclin B. Phil. Trans. R. Soc.  Lond. 354, 1501-1511.

 

12.             Hershko, A., Ciechanover, A. and Varshavsky, A. (2000). The ubiquitin system. Nature Medicine 6, III-XI (Commentary).