BAG-1M: a potential specificity determinant of corticosteroid receptor action.

BAG-1M is a eukaryotic cochaperone that associates with several proteins, including the glucocorticoid receptor (GR). It down-regulates GR-mediated transactivation by a mechanism that requires its prior recruitment by the liganded receptor from cytoplasm into the nucleus. In the nucleus, it uses a repeated sequence motif ([EEX4]8) at its NH2 terminus to inhibit DNA binding, as well as transactivation functions of the receptor. The mineralocorticoid receptor (MR), a structural and functional homologue of the GR, is unable to translocate BAG-1M into the nucleus, and its transactivation function is also not affected by this protein. This differential regulation of GR and MR activity could be relevant in classic mineralocorticoid tissues such as the kidney in which GR activity needs to be repressed to allow the MR to exert its action. In in situ hybridization studies, we show that BAG-1M is expressed in the kidney. Its expression pattern, especially in the developing kidney, correlated well with that of the GR. We therefore postulate that BAG-1M may be a specificity determinant in GR and MR action, and may feature prominently in the control of GR activity in kidney development.