Ubiquitin is a novel substrate for human insulin-degrading enzyme.

ABSTRACT: Insulin-degrading enzyme (IDE) can degrade insulin and amyloid-β, peptides involved in diabetes and Alzheimer's disease, respectively. IDE selects its substrates based on size, charge, and flexibility. From these criteria, we predict that IDE can cleave and inactivate ubiquitin (Ub). Here, we show that IDE cleaves Ub in a biphasic manner, first, by rapidly removing the two C-terminal glycines (k(cat)=2 s(-1)) followed by a slow cleavage between residues 72 and 73 (k(cat)=0.07 s(-1)), thereby producing the inactive 1-74 fragment of Ub (Ub1-74) and 1-72 fragment of Ub (Ub1-72). IDE is a ubiquitously expressed cytosolic protein, where monomeric Ub is also present. Thus, Ub degradation by IDE should be regulated. IDE is known to bind the cytoplasmic intermediate filament protein nestin with hi

SUBMITTER: Ralat LA 

PROVIDER: S-EPMC3064465 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature