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Expression and Degradation of Androgen Receptor: Mechanism and Clinical Implication

George Whipple Laboratory for Cancer Research, Departments of Pathology and Urology, and Cancer Center, University of Rochester Medical Center, Rochester, New York 14642

Address all correspondence and requests for reprints to: Dr. Chawnshang Chang, University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, New York 14642. E-mail: chang{at}urmc.rochester.edu.

The androgen-androgen receptor (AR) signaling pathway plays a key role in proper development and function of male reproductive organs, such as prostate and epididymis, as well as nonreproductive organs, such as muscle, hair follicles, and brain. Abnormalities in the androgen-AR signaling pathway have been linked to diseases, such as male infertility, Kennedy’s disease, and prostate cancer. Regulation of AR activity can be achieved in several different ways: modulation of AR gene expression, androgen binding to AR, AR nuclear translocation, AR protein stability, and AR trans-activation. This review covers mechanisms implicated in the control of AR protein expression and degradation, and their potential linkage to the androgen-related diseases. A better understanding of such mechanisms may help us to design more effective androgens and antiandrogens to battle androgen-related diseases.

This work was supported by NIH Grants DK-60905 and DK-60948 and the George Whipple Professorship Endowment.

Abbreviations: AF-1, Activation function-1; AR, androgen receptor; ARE, androgen response element; ARKO, androgen receptor knockout; CAT, chloramphenicol transferase; CP-1, poly(C)-binding protein-1; CRE, cAMP response element; DBD, DNA-binding domain; DHT, 5-dihydrotestosterone; ER, estrogen receptor; HuR, Hu protein R; LBD, ligand-binding domain; NF-B, nuclear factor-B; PEST, proline-, glutamate-, serine-, and threonine-rich; PI3K, phosphatidylinositol-3-hydroxy kinase; PR, progesterone receptor; PSA, prostate-specific antigen; PTEN, phosphatase and tensin homolog deleted from chromosome 10; SBMA, spinal bulbar muscular atrophy; SRC-1, steroid receptor coactivator; T, testosterone; UTR, untranslated region; VES, vitamin E succinate.

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