Author:

Keywords:

Animals, COS Cells, Hela Cells, Humans, Proteasome Endopeptidase Complex, Receptors, Androgen, Research Support, Non-U.S. Gov't, Trans-Activation (Genetics), Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, Medicine, Research & Experimental, Multidisciplinary Sciences, Research & Experimental Medicine, Science & Technology - Other Topics, androgen receptor, hinge region, proteasome, PEST sequence, transcription regulation, BINDING DOMAIN, DNA-BINDING, TRANSACTIVATION, SEQUENCES, CELLS, ELEMENT, SITES, HeLa Cells, Transcriptional Activation, General Science & Technology

Abstract:

To investigate the function of the hinge region in transcriptional activation by the androgen receptor, we compared the actions of the wild-type receptor with a mutant receptor, deleted of amino acids 628-646 of the hinge. The role of the proteasome on the expression and activity of these two proteins was investigated. The deletion mutant demonstrated a threefold increase in transcriptional activity when compared to the wild-type receptor protein. Furthermore, we found that hormone-dependent stabilization of the receptor protein was more enhanced for the deletion mutant. In addition, experiments using the proteasome inhibitor, MG132, demonstrated that the deletion mutant is more sensitive to proteasome-mediated degradation than the wild-type receptor. However, inhibition of the proteasome had a negative effect on the transcriptional activity of the deletion mutant. Taken together, our results suggest that the hinge region not only plays an important role in controlling the transactivation potential of the androgen receptor but also in determining the influence of the proteasome on androgen receptor-mediated transcriptional activation.