Copine-I: Modulator of NF-kappa B Transcription and Prostate Cancer Survival
Abstract
NF-kB is a dynamic transcription factor that regulates important biological processes involved in cancer initiation and progression. This is especially true in prostate cancer (PCa) where dysregulated NF-kB activity is directly associated with PCa relapse. Identifying regulators that control the half-life of NF-kB is important to understanding molecular processes that control the duration of transcriptional responses. In this the initial funding period, we identify Copine-I, a calcium phospholipid binding protein, as a novel repressor that physically interacts with p65 to inhibit NF-kB transcription. siRNA knockdown of Copine-I increases tumor necrosis factor (TNF) alpha-stimulated NF-kB transcription, while Copine-I expression blocks endogenous transcription. Our work provides evidence that Copine-I regulates the half-life of NF-kB transcriptional responses through a novel mechanism that antagonizes typical polyubiquitination of p65.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2007
- Accession Number
- ADA487021
Entities
People
- Carl Creutz
- Marty W Mayo
Organizations
- University of Virginia