Separate domains of MBP-1 involved in c-myc promoter binding and growth suppressive activity.
We previously demonstrated that exogenous expression of MBP-1 induces rapid cell death in murine fibroblasts, and alters loss of anchorage-independent growth and tumorigenicity in human breast carcinoma cells. Here, we investigated the functional role of two different domains of MBP-1. A DNA-protein interaction study suggested that the amino-terminal half (amino acids 1-178) of MBP-1 possesses the c-myc P2 promoter binding activity. The same domain of MBP-1 also showed transcriptional repressor activity on c-myc promoter by in vitro transient expression assay. On the other hand, the carboxy terminal half (amino acids 190-335) of MBP-1 induced cell death in murine fibroblasts similar to full length MBP-1. Furthermore, exogenous protein expression from the carboxy terminal half of MBP-1 in human breast carcinoma (MCF-7) cells showed suppression of colony formation and loss of anchorage-independent growth. Results from this study suggest that MBP-1 exerts its biological effect through different functional domains.
Ray
R B
RB
Department of Internal Medicine, Saint Louis University, MO 63110, USA. rayrb@sluvca.slu.edu
Steele
R
R
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D006801:Humans; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase