Protein Interaction with the N-Terminus of the Androgen Receptor

Abstract

Abstract : This project, which began with the goal of identifying proteins that bind to the human androgen receptor (hAR) differentially based on the length of the CAG repeat sequence, has been instrumental in revealing new biological findings of the role of the androgen receptor in prostate cancer progression to androgen-independence. Three significant findings were these: 1) Failure to identify any binding proteins for the Gln repeat region of the human androgen receptor. Our conclusion was that the continued search for such binding proteins is not warranted at this time, however further study of ARA24 is warranted. 2) The role of the RB pathway growth arrest in the androgen response in prostate cancer. The occurrence of cell death following the growth arrest, may provide a biology that can be exploited for prostate cancer patient therapy. 3) Bag1L binds to hAR is induced by gain-of-function p53 mutants, and contributes to androgen-independent growth of prostate cancer cells. We believe these findings make important and extremely valuable contributions toward understanding the role of the androgen receptor in hormone-refractory prostate cancer. These multiple findings provide clearer foundations on which to build and propose new projects for study of this important aspect of human prostate cancer.