Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.56 (
insulin-degrading enzyme
)
737
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A major metabolic effect of insulin is inhibition of cellular proteolysis, but the proteolytic systems involved are unclear. Tissues have multiple proteolytic systems, including the ATP- and ubiquitin-dependent proteasome pathway. The effect of insulin on this pathway was examined in vitro and in cultured cells. Insulin inhibited ATP- and ubiquitin-dependent lysozyme degradation more than 90% by reticulocyte extract, in a dose-dependent manner (IC50 approximately 50 nM). Insulin did not reduce the conjugation of ubiquitin to lysozyme and was not itself ubiquitin-conjugated. In HepG2 cells, insulin increased ubiquitin-conjugate accumulation 80%. The association between the 26S proteasome and an intracellular protease, the
insulin-degrading enzyme
(
IDE
), was examined by a purification scheme designed to enrich for the 26S proteasome. Copurification of
IDE
activity and immunoreactivity with the proteasome were detected through several chromatographic steps.
Glycerol
gradient analysis revealed cosedimentation of
IDE
with the 20S proteasome and possibly with the 26S proteasome. The proteasome-associated
IDE
was displaced when the samples were treated with insulin. These results suggest that insulin regulates protein catabolism, at least in part, by decreasing ubiquitin-mediated proteasomal activity, and provides a new target for insulin action. The displacement of
IDE
from the proteasome provides a mechanism for this insulin action.
...
PMID:Insulin inhibits the ubiquitin-dependent degrading activity of the 26S proteasome. 1087 52
