Accession Number : ADA323557
Title : Identification of Novel Candidate Tumor Suppressor Genes Using C. elegans as a Model.
Descriptive Note : Annual rept. 1 Nov 95-31 Oct 96,
Corporate Author : CALIFORNIA INST OF TECH PASADENA
Personal Author(s) : Sternberg, Paul W.
PDF Url : ADA323557
Report Date : NOV 1996
Pagination or Media Count : 26
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 proto oncogene cbl, sli-1, inhibits Ras activation by epidermal growth factor receptor homolog LET-23. Functional domains of SLI-1 were analyzed in transgenic nematodes. The rok-1 gene was also shown to regulate Ras activation. The rok-1 locus was cloned and shown to encode a novel tyrosine kinase with protein protein interaction domains. ROK-1 protein physically interacts with the adaptor protein SEM-5, and thus might exert its negative effect both by being recruited to the EGF-receptor signaling complex and by preventing SEM-5 from leading to ras activation. New screens for additional negative regulators have been initiated to find partners for the SLI-1 and ROK-1. Human homologs of ROK-1 will now be sought.
Descriptors : *NEOPLASMS, *INHIBITORS, *SUPPRESSORS, *BREAST CANCER, ACTIVATION, GENES, CLONES, MOLECULE MOLECULE INTERACTIONS, GENETICS, TYROSINE, PHOSPHORYLATION, PHOSPHORUS TRANSFERASES.
Subject Categories : Biochemistry
Genetic Engineering and Molecular Biology
Medicine and Medical Research
Distribution Statement : APPROVED FOR PUBLIC RELEASE