Obstructing Androgen Receptor Activation in Prostate Cancer Cells through Posttranslational Modification by NEDD8

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2012
Accession Number
ADA566211

Entities

People

  • Don Chen

Organizations

  • Robert Wood Johnson Medical School

Tags

DTIC Thesaurus Topics

  • Androgen Receptors
  • Androgens
  • Biomedical Research
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Culture Media
  • Department Of Defense
  • Electronic Mail
  • Gene Expression
  • Information Operations
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins
  • Sex Hormones

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.
  • Prostate Cancer Biology.