We have identified a gene from human cervical carcinoma (HeLa) cell complementary DNA expression library which was initially characterized as a c-myc promoter binding protein (MBP-1). This protein binds to the upstream region of the human c-myc P2 promoter and negatively regulates c- myc transcription. Subsequent studies on the biological role of this cloned gene showed induction of cell death in fibroblast cells, loss of anchorage- independent growth, reduced invasive ability, and tumorigenicity of human breast carcinoma cells. Growth control is closely associated with abnormal proliferation and tumor suppression. Negative regulatory genes play an important role in cell growth. The cellular gene encoding MBP-1 has some very interesting and significant biological properties relating to inhibition of normal cell proliferation and in controlling malignant phenotype. MBP-1 is a relatively recently identified gene regulatory protein. As an extension of our preliminary work, further studies are necessary for biochemical characterization of MBP-1 and to elucidate the molecular basis of cell growth regulation by this protein. This research proposal is designed to address the following specific aims: 1. Characterization of the tumor suppressor domain of MBP-1 2. Cellular localization and biochemical characterization of MBP-1 3. Identification of the c-myc promoter binding domain in MBP-1 4. Interaction of MBP-1 with cellular protein(s) Thus, understanding the role and regulation of this cellular gene may provide future therapeutic modalities of gene regulation in malignancy.
