Regulation of c-Myc Transcriptional Activity and Function

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DESCRIPTION (provided by applicant): A critical role of c-Myc is to regulate cell cycle progression and apoptosis and the disruption of this regulation has been shown to lead to transformation and tumorigenesis. Preliminary data has revealed a novel c-Myc binding protein, B23 that regulates c-Myc localization and c-Myc transcriptional activity. B23 also significantly enhances c-Myc-induced hyperproliferation and transformation, while also regulating c-Myc-mediated apoptosis. Based on our preliminary studies presented in this proposal, our hypothesis is that direct B23 interaction with c-Myc stimulates the oncogenic activities of c-Myc protein during tumorigenesis by regulating the transcriptional activity and localization of c-Myc. We propose that disruption of this interaction could be the basis of an effective treatment for colon cancer. To test this hypothesis, we will perform the following aims: 1) Characterize the interaction between c-Myc and B23 proteins, 2) Determine the molecular mechanism that mediates the regulation of c-Myc activities by B23 protein and 3) Determine the biological role of B23 interacting with c-Myc. We will also begin testing new treatments to inhibit colon cancer cell proliferation based on our preliminary findings. These studies will have major implications for understanding the function of c-Myc in cell cycle progression and apoptosis and in the treatment of cancer.