Identification of Novel Candidate Tumor Suppressor Genes Using C. Elegans as a Model.
Abstract
Molecular and genetic analysis in the model organism Caenorhabditis elegans was used to identify new negative regulators of tyrosine kinase/ras mediated signal transduction pathways that are candidate tumor suppressors. A nematode homolog of the cbl proto-oncogene was shown to act by regulating activation of Ras by an epidermal growth factor receptor homolog (LET-23). The rok-1 (regulator of kinase-mediated signaling) locus of C. elegans was molecularly cloned by correlating genetic and physical maps and rescue of mutant phenotypes in transgenic nematodes. A new locus, rok-2 was identified in a genetic screen for mutations that hyperactivate the LET-23 signaling pathway in the absence of SLI-1 function. Genetic interactions among these nematode negative regulatory mutations were examined by the construction of multiple mutant strains; these results suggest that multiple pathways regulate the tyrosine kinase/ras signal transduction. These results will help elucidate the function of the cbl family of proto- oncogenes, and to identify novel candidate tumor suppressor loci.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 29, 1995
- Accession Number
- ADA301625
Entities
People
- Paul W. Sternberg
Organizations
- California Institute of Technology