Analysis of the Mechanism of Action of RPF1: Potentiator of Progesterone Receptor and p53-dependent Transcriptional Activity
Abstract
Our interest in proteins which modulate the transcriptional activity of members of the nuclear receptor superfamily led to the identification of yeast RSP5 and its human homolog hRPF1/Nedd4, which potentiate progesterone receptor (PR)-dependent transcription. Subsequently, we have observed that hRPF1 is a potentiator of p53-dependent transcriptional activation. As hRPF1 appears to modulate two transcription factors known to play a role in breast cancer, we are interested in the identification of substrates of hRPF1's enzymatic activity which may explain its transcriptional effect. hRPF1 shares sequence homology with a known family of 'hect' E3 ubiquitin ligases. Both hRPF1 and its yeast homolog, RSP5, have been shown to bind to and ubiquitinate the large subunit of RNA polymerase II. We postulate that there may be additional hRPF1 substrates, the identification of which will help to explain our observations linking E3 ubiquitin ligase activity and the general transcriptional machinery. Using a yeast two-hybrid approach, we have identified a 68 kDa pre-mRNA cleavage factor which specifically binds to and serves as a ubiquitination substrate for hRPF1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADB259887
Entities
People
- Maria R. Huacani
Organizations
- Duke University Hospital