Identification of Novel Candidate Tumor Suppressor Genes Using C. Elegans as a Model.
Annual rept. 1 Nov 94-31 Oct 95,
CALIFORNIA INST OF TECH PASADENA
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Molecular and genetic analysis in the model organism Caenorhabditis elegans was used to identify new negative regulators of tyrosine kinaseras 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 kinaseras signal transduction. These results will help elucidate the function of the cbl family of proto- oncogenes, and to identify novel candidate tumor suppressor loci.
- Anatomy and Physiology
- Genetic Engineering and Molecular Biology