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