Modulation of protein degradation in mammalian cells by ligands and stress.
Two types of environmental effect on intracellular proteolysis in mammalian cells are surveyed. One is the effect of products on the in vivo half-lives of certain enzymes. The other is the effect of stress on the degradation of cellular proteins. The degradation rates of glutamine synthetase (GS), ornithine decarboxylase (ODC) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase are markedly accelerated by their products. The ligand binding sites responsible for the product-accelerated degradation of the enzymes are unknown. In all three cases the labilizing effect of the product molecule is not due to its attachment to the catalytic site. The modes of action of product molecules on GS and ODC degradation have many features in common. Heat shock or other stress cause damage to cellular proteins and induce the synthesis of a small set of heat shock proteins (hsp). Many stressing agents or conditions also accelerate the breakdown of cellular proteins. Current evidence supports the view that the ubiquitin system is responsible for the disposal of aberrant proteins formed by stress. Many observations support the hypothesis that hsp gene expression is induced when abnormal proteins are produced in amounts that exceed the cell's degradative capacity. However, it is still not clear how aberrant proteins induce hsp.
Kulka
R G
RG
Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
D000818:Animals; D015153:Blotting, Western; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000502:physiology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism
D006360:Heat-Shock Proteins; D011506:Proteins; D014452:Ubiquitins; D006903:Hydroxymethylglutaryl CoA Reductases; D009955:Ornithine Decarboxylase; D005974:Glutamate-Ammonia Ligase