T. Miyashita et al., BCL-2 RELIEVES THE TRANS-REPRESSIVE FUNCTION OF THE GLUCOCORTICOID RECEPTOR AND INHIBITS THE ACTIVATION OF CPP32-LIKE CYSTEINE PROTEASES, Biochemical and biophysical research communications, 233(3), 1997, pp. 781-787
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.