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.

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.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Animals, Apoptosis, COS Cells, Cell Division, Cercopithecus aethiops, Cloning, Molecular, Conserved Sequence, Escherichia coli, Gene Expression Regulation, Genes, Tumor Suppressor, Heat-Shock Proteins, Humans, Mice, Mice, Nude, Oxidative Stress, Peroxidases, Peroxiredoxins, Plasmids, Polymerase Chain Reaction, Protein Biosynthesis, Proto-Oncogene Proteins c-myc, Rats, Recombinant Proteins, Saccharomyces cerevisiae, Transfection
J. Biol. Chem.
Date: Nov. 08, 2002
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