Involvement of Novel Multifunction Steroid Hormone Receptor Coactivator, E6-Associated Protein, in Prostate Gland Tumorigenesis
Abstract
E3 ubiquitin-protein ligase enzyme, E6-associated protein (E6-AP), is a novel dual function steroid hormone receptor coactivator. E6-AP not only interacts with and enhances the hormone-dependent transcriptional activities of various steroid hormone receptors, including androgen receptor (AR), but also is a member of the E3 class of functionally related ubiquitin-protein ligases. Previously, using E6-AP knockout animals we have shown that E6-AP is required for the proper development and growth of prostate gland. Previously I have shown that E6-AP regulates PI3K-Akt pathway in the prostate gland and as well as LNCaP cells. In this report I have provided evidence that E6-AP plays a vital role in the prostate gland growth and prostate cancer cell proliferation. E6-AP by itself can modulate p53 levels in prostate cancer cells independent of E6. Our data also indicates that over expression of E6-AP could potentially lead to tumor initiation. I have also shown that E6-AP also affects the non-genomic mechanisms of AR. ChIP assays demonstrate that AR is accumulated on its target promoter and enhancer under E6-AP knockdown conditions. Taken together, these studies indicate that E6-AP plays a vital role in both the genomic and non-genomic signaling pathway of AR and their downstream effectors might play critical roles in many biological processes, especially in cell growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2010
- Accession Number
- ADA524513
Entities
People
- Sathish Srinivasan
Organizations
- University of Miami