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.
Section of Hematology/Oncology, The Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Zhao Mei
ZM
Mu
Xiao Ying
XY
Yin
Edward V
EV
Prochownik
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002455:Cell Division; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004926:Escherichia coli / Q000235:genetics; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018384:Oxidative Stress / Q000502:physiology; D010544:Peroxidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D010957:Plasmids; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014162:Transfection
D006360:Heat-Shock Proteins; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D010544:Peroxidases; C489898:Prdx1 protein, rat; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse