Retinoblastoma protein is functionally distinct from its homologues in affecting glucocorticoid receptor-mediated transcription and apoptosis

The cell cycle regulator, retinoblastoma protein, is known to potentiate gl ucocorticoid receptor-activated transcription through the interaction of it s pocket domain with the transcription coactivator, hBRM. We now show that glucocorticoid receptor-induced apoptosis is also dependent on both the ret inoblastoma protein and hBRM. p107 and p130, which share extensive sequence homology with the pocket domain of the retinoblastoma protein but not its N-terminal region, also interact with hBRM but do not support either glucoc orticoid receptor-dependent activity. This difference arises from the diver gent N-terminal domain of the retinoblastoma protein, which, when fused to the pocket domains, confers upon p107 and p130 the ability to influence glu cocorticoid receptor activities. This effect probably results from the prom otion of glucocorticoid receptor-targeted chromatin remodeling by the hBRM- containing SWI/SNF complex because the N-terminal domain of the retinoblast oma protein enhances glucocorticoid receptor-hBRM interactions. These resul ts highlight that, besides the interaction between hBRM and the pocket; dom ain. of RE, the N-terminal region of the retinoblastoma protein is also ess ential for; glucocorticoid receptor-induced apoptosis and the potentiation of glucocorticoid receptor-mediated transcription and provide a basis for f unctional distinction between the retinoblastoma protein and its homologues .