title: Bcl-2 relieves the trans-repressive function of the glucocorticoid receptor and inhibits the activation of CPP32-like cysteine proteases.
abstract: Glucocorticoid induces apoptosis in immature lymphocytes which is inhibitable by Bcl-2. Although glucocorticoid-mediated signal transduction is well understood, the mechanism of the induction of apoptosis by the activated glucocorticoid receptor as well as the inhibition of apoptosis by Bcl-2 remains enigmatic. Here we report that overexpressed Bcl-2 relieves the glucocorticoid receptor-mediated repressive function on the AP-1 activity and completely inhibits the activation of CPP32-like cysteine proteases. In contrast, glucocorticoid receptor-mediated transactivation was not affected by Bcl-2. This suggests that glucocorticoid may induce apoptosis by repressing transactivation by AP-1 which is relieved by Bcl-2. Furthermore, we report evidence that, in contrast with CPP32-like proteases, ICE-like proteases are not involved in this apoptotic pathway.
authors.affiliation: Department of Genetics, National Children's Medical Research Center, Tokyo, Japan. tmiyashita@nch.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Miyashita
authors.forename: U
authors.initials: U
authors.lastname: Mami
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
authors.forename: M
authors.initials: M
authors.lastname: Yamada
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation; D015870:Gene Expression; D019254:Genes, bcl-2; D006367:HeLa Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D017931:DNA Primers; D019253:Proto-Oncogene Proteins c-bcl-2; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1