The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation.
Deregulated expression of the c-Myc transcription factor is found in a wide variety of human tumors. Because of this significant role in oncogenesis, considerable effort has been devoted to elucidating the molecular program initiated by deregulated c-myc expression. The primary transforming activity of Myc is thought to arise through transcriptional regulation of numerous target genes. Thus far, Myc target genes involved in mitochondrial function have not been characterized in depth. Here, we describe a nuclear c-Myc target gene, PRDX3, which encodes a mitochondrial protein of the peroxiredoxin gene family. Expression of PRDX3 is induced by the mycER system and is reduced in c-myc(-/-) cells. Chromatin immunoprecipitation analysis spanning the entire PRDX3 genomic sequence reveals that Myc binds preferentially to a 930-bp region surrounding exon 1. We show that PRDX3 is required for Myc-mediated proliferation, transformation, and apoptosis after glucose withdrawal. Results using mitochondria-specific fluorescent probes demonstrate that PRDX3 is essential for maintaining mitochondrial mass and membrane potential in transformed rat and human cells. These data provide evidence that PRDX3 is a c-Myc target gene that is required to maintain normal mitochondrial function.
Wonsey
Diane R
DR
Program in Human Genetics and Molecular Biology and Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zeller
Karen I
KI
Dang
Chi V
CV
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D010544:Peroxidases / Q000235:genetics / Q000378:metabolism*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
C516116:Prdx3 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D010544:Peroxidases; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins