Abstract

The energy-dependence of intracellular protein breakdown has been recognized for a long time, but the biochemical mechanisms of this process remained unknown. We are investigating the mechanisms of protein breakdown in an ATP-dependent proteolytic system from reticulocytes. The system has been resolved into several essentially required components. One of these, a heat-stable polypeptide designated as APF-1 (ATP-dependent Proteolysis Factor 1) becomes conjugated to proteins in an ATP-requiring reaction. The polypeptide appears to be identical with ubiquitin, a universally occurring polypeptide of unknown function. The present work examines the role of the conjugation of ubiquitin with proteins in protein breakdown, by delineating the enzymatic processes carrying out the formation and the breakdown of ubiquitin-protein conjugates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM025614-06
Application #
3151526
Study Section
Biochemistry Study Section (BIO)
Project Start
1980-02-01
Project End
1986-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Technion-Israel Institute of Technology
Department
Type
DUNS #
City
Haifa
State
Country
Israel
Zip Code
32000

  Publications

Eytan, E; Ganoth, D; Armon, T et al. (1989) ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin. Proc Natl Acad Sci U S A 86:7751-5
Reiss, Y; Heller, H; Hershko, A (1989) Binding sites of ubiquitin-protein ligase. Binding of ubiquitin-protein conjugates and of ubiquitin-carrier protein. J Biol Chem 264:10378-83
Reiss, Y; Kaim, D; 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 263:2693-8
Hershko, A (1988) Ubiquitin-mediated protein degradation. J Biol Chem 263:15237-40
Ganoth, D; Leshinsky, E; Eytan, E et al. (1988) A multicomponent system that degrades proteins conjugated to ubiquitin. Resolution of factors and evidence for ATP-dependent complex formation. J Biol Chem 263:12412-9
Raviv, O; Heller, H; Hershko, A (1987) Alterations in components of the ubiquitin-protein ligase system following maturation of reticulocytes to erythrocytes. Biochem Biophys Res Commun 145:658-65
Hershko, A; Rose, I A (1987) Ubiquitin-aldehyde: a general inhibitor of ubiquitin-recycling processes. Proc Natl Acad Sci U S A 84:1829-33
Hershko, A; Heller, H; Eytan, E et al. (1986) The protein substrate binding site of the ubiquitin-protein ligase system. J Biol Chem 261:11992-9
Hershko, A; Ciechanover, A (1986) The ubiquitin pathway for the degradation of intracellular proteins. Prog Nucleic Acid Res Mol Biol 33:19-56, 301
Hershko, A (1985) The ATP-ubiquitin proteolytic pathway. Prog Clin Biol Res 180:11-6

Showing the most recent 10 out of 11 publications