An Estrogen Receptor-Selective Coactivator: A Potential Regulator of Tamoxifen Effectiveness in Breast Cancer Treatment and Prevention
Abstract
The estrogen receptor (ER) is involved in breast cancer development and progression. We have isolated a novel 97 kDa DEAD box RNA helicase (DP97) that interacts with the estrogen receptor alpha (ERa) in the presence of either estradiol or trans-hydroxytamoxifen. DP97 represses the transcriptonal activity of the estradiol-occupied estrogen receptor and this repression can be relieved with Trichostatin A(TSA), a selective histone deacetylase inhibitor. DP97 represses the activity of a constitutive SV4O promoter when it is recruited as a Gal-4 DNA binding domain fusion protein. DP97 also interacts with, and represses the activity of, other nucelar receptors such as the progesterone receptor b, glucocorticoid receptor, and retionic acid receptor a. However, DP97 does not repress the activity of either p53 or VP16. We show that the N- terminal helicase region of DP97 is dispensible for its activity as a transcriptional repressor. Furthermore, a BLAST homology search of the remaining sequence of p97 reveales that this protein has a small region of homology with the SMRTe(NCoR2) corepressor protein. This small region is also able to repress a constitutively active SV4O promoter when it is recmited to it as a Gal-4 DNA binding domain fusion protein. Therefore, DP97 functions as a RNA helicase, a nuclear receptor interacting protein, and as a transcriptional coregulator.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA410346
Entities
People
- Ramji R. Rajendran
Organizations
- University of Illinois Urbana–Champaign