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Obstructing Androgen Receptor Activation in Prostate Cancer Cells through Posttranslational Modification by NEDD8
Annaul rept. 15 Apr 2011-14 Apr 2012
ROBERT WOOD JOHNSON MEDICAL SCHOOL PISCATAWAY NJ
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Androgen receptor AR mediates the action of male sex hormones and plays a crucial role in the therapy of prostate cancer. Post-translational modification has significant impacts on gene expression, but how it affects AR activity is largely unknown. In this study, we demonstrate that AR is covalently modified by NEDD8. We show that PIASy is the E3 ligase catalyzing AR neddylation. We also find that Jab1 interacts with AR and enhances its transcriptional activity through de-neddylation. In the past year, we further established Jab1 shRNA expressing cell lines and characterized the effects of Jab1 silencing on prostate cancer cell growth and proliferation. We show that silencing of Jab1 inhibits prostate cancer cell proliferation.
APPROVED FOR PUBLIC RELEASE