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 glucocorticoid receptor-activated transcription through the interaction of its pocket domain with the transcription coactivator, hBRM. We now show that glucocorticoid receptor-induced apoptosis is also dependent on both the retinoblastoma 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 glucocorticoid receptor-dependent activity. This difference arises from the divergent N-terminal domain of the retinoblastoma protein, which, when fused to the pocket domains, confers upon p107 and p130 the ability to influence glucocorticoid receptor activities. This effect probably results from the promotion of glucocorticoid receptor-targeted chromatin remodeling by the hBRM-containing SWI/SNF complex because the N-terminal domain of the retinoblastoma protein enhances glucocorticoid receptor-hBRM interactions. These results highlight that, besides the interaction between hBRM and the pocket domain of RB, the N-terminal region of the retinoblastoma protein is also essential for glucocorticoid receptor-induced apoptosis and the potentiation of glucocorticoid receptor-mediated transcription and provide a basis for functional distinction between the retinoblastoma protein and its homologues.