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Binding proteins dissociate upon ligand binding Receptor-Binding Proteins APC in GI Cancers ! FAP due to germline mutations in APC ! Somatic (sporadic) mutations in the APC gene initiate colorectal malignancy ! APC mutations in 63% of colonic adenomas ! 99% of germline and 100% of sporadic APC mutations lead to truncated protein Significance of Signal Transduction to Disease: Tumorigenesis ● ● Cancer cells contain genetic damage many of the genes encoding signaling molecules have been shown to be capable of causing cancer if disrupted in some way APC Function !

CML results from a translocation between chromosomes 9 and 22 ! Result is termed the Ph+ chromosome ! ABL gene on chromosome 9 placed next to BRC gene on 22 results in a fusion protein bcr-abl ! abl is a non-receptor Y-kinase ! bcr is member of the Rho family of small GTPases ! Similar translocation occurs in ALL CML is target of Y-kinase inhibitor Glivec Non-Hodgkin’s Lymphoma ! ! !

Result is termed the Ph+ chromosome ! ABL gene on chromosome 9 placed next to BRC gene on 22 results in a fusion protein bcr-abl ! abl is a non-receptor Y-kinase ! bcr is member of the Rho family of small GTPases ! Similar translocation occurs in ALL CML is target of Y-kinase inhibitor Glivec Non-Hodgkin’s Lymphoma ! ! !

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