Targeting of Oncogenic Proteins for Intracellular Degradation (97breast)
Abstract
Selective depletion of intracellular oncogenic proteins is a potentially powerful tool for the treatment of breast cancer. This is usually achieved by genetic manipulation of the target gene using procedures such as gene disruption, antisense or ribozyme technologies. We now propose an alternative approach in which an oncogenic protein is specifically targeted for intracellular degradation. In order to do this we will take advantage of the permeability properties of the third helix of the antennapedia protein. This will be used to deliver a small trifunctional peptide consisting of a target protein binding peptide and a peptide designed to interact with the E2 class of ubiquitin conjugating enzymes. In this way the ubiquitin-conjugating machinery will be selectively recruited to the target protein which should then be degraded by the proteosome. We have used the transmembrane tyrosine kinase ErbB-2 as a model system since its oncogenic activity is * regulated at the level of protein stability and it is clearly important in breast cancer. Targeting constructs have been made and expressed in cells of varying ErbB-2 status.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA385270
Entities
People
- Stephen W. Byers
Organizations
- Georgetown University