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

作者：Z M Mu, Xiao Ying Yin, Edward V. Prochownik · 发表于：Journal of Biological Chemistry · 年份：2002 · DOI：10.1074/jbc.m206066200 · 被引用次数：141 · 研究领域：Redox biology and oxidative stress、Protein Kinase Regulation and GTPase Signaling、Melanoma and MAPK Pathways

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.