Identification of Novel Candidate Tumor Suppressor Genes Using C. elegans as a Model.
Abstract
Molecular genetic analysis of the model organism Caenorhabditis elegans was used to identify and study mechanisms of action of negative regulators of tyrosine kinase/ras mediated signal transduction that are candidate tumor suppressors. A homolog of the proto oncogene cbl, SLI-1, inhibits Ras activation by the epidermal growth factor receptor homolog LET-23. The domain of human c-cbl most highly conserved functions in C. elegans when substituted for the homologous region of SLI-1. Proteins that interact with this region of SLI-1 have been identified by a "two-hybrid" screen in yeast. ROK-1, a novel tyrosine kinase, has been characterize. Both SLI-1 and ROK-1 have proline-rich domains that are necessary for their function. New screens for additional negative regulators have identified at least three genes that are now being analyzed. Human homologs of ROK-1 are now being sought.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1997
- Accession Number
- ADA344938
Entities
People
- Paul W. Sternberg
Organizations
- California Institute of Technology