Activity-dependent COX-2 proteolysis modulates aerobic respiration and proliferation in a prostaglandin-independent manner.

ABSTRACT: Cyclooxygenase-2 (COX-2) catalyzes the oxidation of arachidonic acid (AA) into a single product that is the source of all prostaglandins (PGs), ligands of multiple pro-inflammatory pathways. AA catalysis results in suicide inactivation, rendering the enzyme catalytically inactive. Here, we report that catalytic activity also leads to controlled cleavage of COX-2, an event that is differentially regulated by fatty acids, and blocked by COX inhibitors. We also find COX-2 fragments in human colon tumors. Using mass spectrometry, we identified two adjacent cleavage points within the catalytic domain, which give rise to COX-2 fragments that are catalytically inactive and localize to different cellular compartments. Expression of one of these fragments in cells significantly reduced mitochondria

SUBMITTER: Hartal-Benishay LH 

PROVIDER: S-EPMC11647142 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature