Proteasome proteolysis supports stimulated platelet function and thrombosis.

ABSTRACT:

Objective

Proteasome inhibitors used in the treatment of hematologic cancers also reduce thrombosis. Whether the proteasome participates in platelet activation or function is unclear because little is known of the proteasome in these terminally differentiated cells.

Approach and results

Platelets displayed all 3 primary proteasome protease activities, which MG132 and bortezomib (Velcade) inhibited. Proteasome substrates are marked by ubiquitin, and platelets contained a functional ubiquitination system that modified the proteome by monoubiquitination and polyubiquitination. Systemic MG132 strongly suppressed the formation of occlusive, platelet-rich thrombi in FeCl3-damaged carotid arteries. Transfusion of platelets treated ex vivo with MG132 and washed before transfusion in

SUBMITTER: Gupta N 

PROVIDER: S-EPMC4059534 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature