| The c-Myc transcription factor is activated in a wide variety of human tumors. Deregulated c-Myc expression induces a global alteration in cellular transcription, leading to transformation. However, the role of many transcriptional targets regulated by c-Myc is unknown. We describe here a nuclear c-Myc target gene, PRDX3, which encodes a mitochondrial protein of the peroxiredoxin gene family. We have characterized PRDX3 expression and found that it is induced by c-Myc in several model systems. In an effort to determine whether PRDX3 is necessary for transformation induced by c-myc, we have generated stable cells lines expressing PRDX3 in either the sense or antisense conformation. PRDX3 antisense cells show a dramatic increase in doubling time compared to cells transfected with empty vector alone. Antisense PRDX3 also inhibits colony formation in semisolid media, as well as inhibiting glucose deprivation-induced apoptosis. Using fluorescent dyes to assess mitochondrial mass and mitochondrial membrane potential, we have found that PRDX3 expression dramatically affects mitochondrial homeostasis. Our results suggest that mitochondrial function is required for c-myc-induced transformation and apoptosis following glucose withdrawal. We describe here the first mitochondrial c-Myc target gene with a biological role in myc-mediated transformation and apoptosis. |
