A Potential Tumor Suppressor Protein: Expression and Function in Human Breast Cancer Cells
Abstract
In a search for genes with a role in hormonal control of cell proliferation, we cloned a novel progestin-induced gene, EDD (previously DD5) that appears to be the human homologue of the hyd tumor suppressor gene of Drosophila melanogaster. By amino acid homology with other known proteins it is likely that the EDD protein is an E3 ubiquitin-protein ligase, enzymes which target one or more key proteins for destruction by ubiquitin-mediated proteolysis. During the first year of this project EDD was shown to be capable of E3 activity and antibodies useful in detecting and characterizing EDD were obtained. To further define the cellular role of EDD eighteen candidate proteins were tested for interaction with EDD by immunoprecipitation. Nine proteins were tested using the yeast two-hybrid system. Yeast two-hybrid screening of cDNA libraries identified eight possible ubiquitination targets for EDD. So far two of these interactions have been confirmed by independent means. Studies of EDD in HEK-293 cells led to the discovery of an additional cellular role for EDD, that of a co-activator for progesterone mediated transcription. Finally experiments to define a possible role for EDD in human cancer have provided exciting data suggesting involvement of the EDD gene in several tumor types.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADA384060
Entities
People
- Michelle J. Callaghan
Organizations
- Garvan Institute of Medical Research