Hemin inhibits ubiquitin-dependent proteolysis in both a higher plant and yeast

Journal Article · Tue May 03 04:00:00 EDT 1988 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00409a025· OSTI ID:7000179

Vierstra, R D; Sullivan, M L

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), Journal Name: Biochemistry; (United States) Vol. 27:9; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
ANIMALS
ATP
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIODEGRADATION
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CEREALS
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
ENZYMES
ERYTHROCYTES
FUNGI
GLYCOSYL HYDROLASES
GRASS
HALIDES
HALOGEN COMPOUNDS
HEME
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROLASES
INHIBITION
INORGANIC PHOSPHORS
INTERMEDIATE MASS NUCLEI
IODIDES
IODINE 125
IODINE COMPOUNDS
IODINE ISOTOPES
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LYSOZYME
MAMMALS
MATERIALS
MICROORGANISMS
NUCLEI
NUCLEOTIDES
O-GLYCOSYL HYDROLASES
OATS
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORS
PIGMENTS
PLANTS
PORPHYRINS
PROTEOLYSIS
RABBITS
RADIOISOTOPES
REACTION KINETICS
RETICULOCYTES
SACCHAROMYCES
SACCHAROMYCES CEREVISIAE
SODIUM COMPOUNDS
SODIUM IODIDES
VERTEBRATES
YEASTS