BCL-2 RELIEVES THE TRANS-REPRESSIVE FUNCTION OF THE GLUCOCORTICOID RECEPTOR AND INHIBITS THE ACTIVATION OF CPP32-LIKE CYSTEINE PROTEASES

Glucocorticoid induces apoptosis in immature lymphocytes which is inhi bitable by Bcl-2. Although glucocorticoid-mediated signal transduction is well understood, the mechanism of the induction of apoptosis by th e activated glucocorticoid receptor as well as the inhibition of apopt osis by Bcl-2 remains enigmatic. Here we report that overexpressed Bcl -2 relieves the glucocorticoid receptor-mediated repressive function o n the AP-1 activity and completely inhibits the activation of CPP32-li ke cysteine proteases, In contrast, glucocorticoid receptor-mediated t ransactivation was not affected by Bcl-2. This suggests that glucocort icoid may induce apoptosis by repressing transactivation by AP-1 which is relieved by Bcl-2. Furthermore, we report evidence that, in contra st with CPP32-like proteases, ICE-like proteases are not involved in t his apoptotic pathway. (C) 1997 Academic Press.