Hemin inhibits ubiquitin-dependent proteolysis in both a higher plant and yeast
In eukaryotes, a major route for ATP-dependent protein breakdown proceeds through covalent intermediates of target proteins destined for degradation and the highly conserved, 76 amino acid protein ubiquitin. In rabbit reticulocytes, it has been shown that hemin effectively inhibits this pathway by blocking the catabolism of ubiquitin-protein conjugates. Here the authors demonstrate that hemin is also an effective inhibitor of the ubiquitin-dependent proteolytic pathway in both a higher plant, oats (Avena sativa), and yeast (Saccharomyces cerevisiae). Hemin inhibits all stages of the pathway in vitro, including ATP-dependent formation of ubiquitin-protein conjugates, disassembly of conjugates by ubiquitin-protein lyase(s) (or isopeptidases), and degradation of ubiquitin-protein conjugates by ATP-dependent protease(s). Using ubiquitin-/sup 125/I-lysozyme conjugates synthesized in vitro as substrates, they determined the specific effects of hemin on the rates of disassembly and degradation separately. The concentration of hemin required for half-maximal inhibition of both processes was identical in each species, approx. 60 ..mu..M in oats and approx. 50 ..mu..M in yeast. Similar inhibitory effects were observed when two hemin analogues, mesoheme or protoporphyrin IX, were employed. These results demonstrate that the effect of hemin on ubiquitin-dependent proteolysis is not restricted to erythroid cells and as a result hemin may be a useful tool in studies of this pathway in all eukaryotic cells. These results also question models where hemin serves as a specific negative modulator of proteolysis in erythroid cells.
- Research Organization:
- Univ. of Wisconsin, Madison (USA)
- OSTI ID:
- 7000179
- Journal Information:
- Biochemistry; (United States), Vol. 27:9
- Country of Publication:
- United States
- Language:
- English
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LABELLED COMPOUNDS
BIODEGRADATION
PROTEOLYSIS
BIOLOGICAL PATHWAYS
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AUTORADIOGRAPHY
ELECTROPHORESIS
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LYSOZYME
OATS
RABBITS
RETICULOCYTES
SACCHAROMYCES CEREVISIAE
SODIUM IODIDES
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ANIMALS
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BIOLOGICAL MATERIALS
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BODY FLUIDS
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DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
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IODINE COMPOUNDS
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NUCLEI
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O-GLYCOSYL HYDROLASES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORS
PIGMENTS
PLANTS
PORPHYRINS
RADIOISOTOPES
REACTION KINETICS
SACCHAROMYCES
SODIUM COMPOUNDS
VERTEBRATES
YEASTS
550201* - Biochemistry- Tracer Techniques