Deacetylation of Androgen Receptor by SIRT2 and its Dysregulation Promotes Pathogenesis and Progression of Prostate Cancer.

Aim: The purpose of the study was to investigate whether the androgen receptor (AR) whose activity is closely associated with prostate cancer is post-translationally regulated by a NAD+ dependent and aging associated protein, sirtuin2 (SIRT2). Material and Method: Immunoprecipitation-Western blotting was conducted to examine the association of the AR and SIRT2 in cultured 293T and LNCaP cells. In addition, we performed in vitro deacetylation assays using purified SIRT2 and AR proteins. Results: SIRT2 gene removal mouse prostate had hyper-acetylated the AR. In vitro and in vivo interaction assays revealed that SIRT2 physically interacted with the AR in prostate cancer cell line LNCaP. Finally, SIRT2 deacetylated the AR in vitro conditions. Conclusion: SIRT2 interacted with the AR and deacetylated it. Identifying partners of the AR and molecular mechanisms of its regulation is curial for understanding the pathogenesis of prostate cancer. Using small molecules to activate SIRT2 might be an important clinical approach to prevent, treat or delay the prostate cancer progression. [ABSTRACT FROM AUTHOR]