The restricted expression of some genes to distinct stages of the cell cycle is often brought about through alterations in the activity and/or abundance of specific transcription factors. Many cells have been shown to be unresponsive to glucocorticoid hormone action during the G phase of the mammalian cell cycle, suggesting that some activities of the glucocorticoid receptor (GR), a ligand-activated transcription factor, are subjected to cell cycle control. We show here that GR insensitivity in G is selective, affecting receptor-mediated transactivation from a simple glucocorticoid response element, but not repression from a composite glucocorticoid response element. Since glucocorticoid-dependent down-regulation of GR protein levels is also unaffected in G, distinct activities of the receptor that participate in this homologous down-regulation must be operating as effectively in G-synchronized cells as in asynchronous cells. Finally, the phosphorylation state of the GR is altered in G-synchronized cells reflecting, in part, both site-specific phosphorylation and dephosphorylation events. These results suggest that, while GR may be a target for cell cycle regulated kinases and phosphatases, the resulting changes in receptor phosphorylation have an impact only on selected GR functions.

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