Pag, a Putative Tumor Suppressor, Interacts with the Myc Box II Domain of c-Myc and Selectively Alters Its Biological Function and Target Gene Expression

• Published in: The Journal of biological chemistry 2002-11, Vol.277 (45), p.43175-43184
• Main Authors: Mu, Zhao Mei, Yin, Xiao Ying, Prochownik, Edward V
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Apoptosis; Cell Division; Chlorocebus aethiops; Cloning, Molecular; Conserved Sequence; COS Cells; Escherichia coli - genetics; Gene Expression Regulation; Genes, Tumor Suppressor; Heat-Shock Proteins - chemistry; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Humans; Mice; Mice, Nude; Oxidative Stress - physiology; Peroxidases - chemistry; Peroxidases - genetics; Peroxidases - metabolism; Peroxiredoxins; Plasmids; Polymerase Chain Reaction; Protein Biosynthesis; Proto-Oncogene Proteins c-myc - chemistry; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Rats; Recombinant Proteins - chemistry; Recombinant Proteins - metabolism; Saccharomyces cerevisiae - genetics; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M206066200

The highly conserved Myc Box II (MBII) domain of c-Myc is critically important for transformation and transcriptional regulation. A yeast two-hybrid screen identified Pag as a MBII-interacting protein. Pag, a member of the peroxiredoxin family, has been reported previously to bind to and inhibit the cytostatic properties of the c-Abl oncoprotein. We now show that Pag promotes increased cell size and confers a proapoptotic phenotype, two hallmark features of ectopic c-Myc overexpression. Pag and c-Myc also confer resistance to oxidative stress, a previously unrecognized property of the latter protein. In contrast, Pag inhibits tumorigenesis by c-Myc-overexpressing fibroblasts and causes a broad but selective loss of c-Myc target gene regulation. Pag is therefore an MBII-interacting protein that can either mimic or enhance some of the c-Myc properties while at the same inhibiting others. These features, along with the previously identified interaction with c-Abl, provide support for the idea that Pag functions as a tumor suppressor.