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 - PubMed (original) (raw)

. 2002 Nov 8;277(45):43175-84.

doi: 10.1074/jbc.M206066200. Epub 2002 Aug 23.

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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

Zhao Mei Mu et al. J Biol Chem. 2002.

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Abstract

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.

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