| The c-Myc oncogenic transcription factor contributes to the development of numerous human malignancies, however the exact role that it plays remains to be elucidated. In order to delineate the various functions of c-myc, our lab carried out a representational difference analysis (RDA) screen to identify putative c-Myc targets. This screen identified JP1, which was subsequently cloned and shown to be directly regulated by c-Myc. In particular, JP1 expression is induced by serum in wild-type fibroblasts, but is not induced in fibroblasts nullizygous for c-myc. Furthermore, the JP1 transcript is induced in Rat1a-MycER cells treated with 4-OH-tamoxifen in the presence of the protein synthesis inhibitor cycloheximide. JP1 mRNA is most highly expressed in the small intestine and thymus, whereas expression is virtually absent in spleen, bone marrow, and peripheral leukocyte. JP1 is a 47 kDa nuclear protein with no significant homologies to any known proteins. In order to determine the role that JP1 plays in c-Myc mediated cellular phenotypes, stable JP1 over-expressing cell lines were created. JP1 transforms Rat1 a cells by inducing anchorage-independent growth, as does c-Myc. Furthermore, JP1 over-expression in CB33 B lymphoblast cells also induces anchorage independent growth in methylcellulose. Intriguingly, over-expression of JP1 does not induce apoptosis or tumorigenesis of Rat1a cells. Our observations define a novel c-Myc target gene that participates in selected c-Myc mediated phenotypes, providing an emerging concept that c-Myc target genes constitute nodal points in a network of pathways that lead from c-Myc to its various related phenotypes. |
