The androgen receptor (AR) is a ligand-dependent transcription factor that has an essential role in the normal growth, development, and maintenance of the prostate gland. The AR is part of a large family of steroid receptors that also includes the glucocorticoid, progesterone, and mineralocorticoid receptors. Steroid receptor family members share significant homology at their DNA and ligand-binding domains. However, these receptors exhibit a high degree of sequence variability at their NH 2 -terminal domain, which suggests the possibility of receptor-specific interactions with co-regulator proteins. Transcriptional co-regulators that interact with the AR may have a role in defining AR activity and may be involved in directing AR-specific responses. Here we have identified Ran-binding protein in the microtubule-organizing center (RanBPM) to be a novel AR-interacting protein by yeast two-hybrid assay and have confirmed this interaction by glutathione S-transferase-and His-tagged pull-down assays. In addition, transient overexpression of RanBPM in prostate cancer cell lines resulted in enhanced AR activity in a liganddependent fashion. Glucocorticoid receptor activity was also enhanced when RanBPM was overexpressed, whereas estrogen receptor activity remained unchanged. These data demonstrate that RanBPM interacts with steroid receptors to selectively modify their activity. The androgen receptor (AR)1 is a ligand-dependent transcription factor that belongs to a family of steroid receptors along with the glucocorticoid (GR), progesterone, and mineralocorticoid receptors. These steroid receptors share similar domain structures and mechanism of action. Steroid receptors including the AR have three functional domains: a COOHterminal ligand-binding domain (LBD), a central DNA-binding domain (DBD), and an NH 2 -terminal domain (1). In the absence of androgens, the AR is localized to the cytoplasm in an inactive complex that includes heat shock proteins (HSP). Upon binding to its cognate ligand, the AR undergoes a conformational change that results in a more compact and stable form of the AR. The activated AR dissociates from HSPs and translocates to the nucleus where it interacts with consensus DNA sequences as a homodimer to influence transcription of downstream genes (2). The estrogen receptor (ER) belongs to a different steroid receptor subfamily because it resides predominantly in the nucleus, even in its unliganded form, and does not require translocation across the nuclear membrane following activation (3). There are two major transactivation regions in the AR. 1) The activation function-1 (AF-1) domain is found at the NH 2 terminus. 2) AF-2 is located in the LBD. AF-2 is a weak transactivator that is dependent on the presence of androgens for its activation. AF-1, on the other hand, is capable of ligand-independent transactivation, and fragments of the AR that contain AF-1 show high levels of transcriptional activity when ectopically expressed in cell lines that are devoid of endogenous AR (4, 5).Upon DNA binding,...
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