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The Hinge Region of the Androgen Receptor Plays a Role in Proteasome‐Mediated Transcriptional Activation
Author(s) -
TANNER TAMZIN,
CLAESSENS FRANK,
HAELENS ANNEMIE
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.068
Subject(s) - androgen receptor , transactivation , mg132 , proteasome , mutant , receptor , 5 ht5a receptor , wild type , enzyme linked receptor , microbiology and biotechnology , spinal and bulbar muscular atrophy , biology , rnf4 , proteasome inhibitor , chemistry , biochemistry , gene expression , gene , genetics , prostate cancer , cancer
A bstract : 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.