Deubiquitinases Modulate Platelet Proteome Ubiquitination, Aggregation, and Thrombosis.

ABSTRACT:

Objective

Platelets express a functional ubiquitin-proteasome system. Mass spectrometry shows that platelets contain several deubiquitinases, but whether these are functional, modulate the proteome, or affect platelet reactivity are unknown.

Approach and results

Platelet lysates contained ubiquitin-protein deubiquitinase activity hydrolyzing both Lys48 and Lys63 polyubiquitin conjugates that was suppressed by the chemically unrelated deubiquitinase inhibitors PYR41 and PR619. These inhibitors acutely and markedly increased monoubiquitination and polyubiquitination of the proteome of resting platelets. PYR41 (intravenous, 15 minutes) significantly impaired occlusive thrombosis in FeCl3-damaged carotid arteries, and deubiquitinase inhibition reduced platelet adhesion and reten

SUBMITTER: Gupta N 

PROVIDER: S-EPMC4662625 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature