Degradation of transglutaminase 2 by calcium-mediated ubiquitination responding to high oxidative stress.

Transglutaminase 2 (TG2) is a calcium-dependent enzyme that catalyzes the transamidation reaction. There is conflicting evidence on the role of TG2 in apoptosis. In this report, we show that TG2 increases in response to low level of oxidative stress, whereas TG2 diminishes under high stress conditions. Monitoring TG2 expression, activity and calcium concentration in cells treated with A23187 revealed that the initial rise of calcium activates TG2 but subsequent calcium-overload induces the degradation of TG2 via calcium-mediated polyubiquitination. These results indicate that the role of TG2 in apoptosis depends on the level of calcium influx triggered by oxidative stress.