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  • Original Article
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Pim kinase-dependent inhibition of c-Myc degradation

Oncogene volume 27, pages 4809–4819 (2008)Cite this article

Abstract

Pim kinases are found to be highly expressed in leukemia, lymphoma, prostate and pancreatic cancer. Bitransgenic mice overexpressing either Pim-1 or Pim-2 and c-Myc succumb to pre-B-cell lymphoma at a strikingly accelerated speed. Despite that Pim-1/Pim-2 has long been recognized as a strong synergistic partner with c-Myc in tumorigenesis, the mechanism underlying the synergism is still not well understood. Overexpression of Pim-1/Pim-2 kinase dramatically stabilizes c-Myc in vivo, and the stabilization is partially mediated by phosphorylation of c-Myc by Pim kinase on a novel site, Ser329. We provide evidence that Pim-2 is more efficient in directly phosphorylating c-Myc Ser329 to stabilize c-Myc. In contrast, we find that Pim-1 is more effective in mediating a decrease in c-Myc Thr58 phosphorylation and an increase in c-Myc Ser62 phosphorylation than in phosphorylating Ser329. In either case, through stabilizing c-Myc, Pim-1/Pim-2 kinases enhance the transcriptional activity of c-Myc. Also knocking down either Pim-1 or Pim-2 dramatically decreases the endogenous levels of c-Myc and thus, its transcriptional activity. Finally, coexpression of the Pim kinases and c-Myc enhances the transforming activity of c-Myc as does the phosphomimic mutant of c-Myc on Ser329. We conclude that these findings appear to explain at least in part the mechanism underlying the synergism between the Pim kinases and c-Myc in tumorigenesis.

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Acknowledgements

This study was supported by grant NIH R01-CA104470. We thank Dr Mark I Greene (School of Medicine, University of Pennsylvania) for providing us the luciferase reporter plasmid, pM4 min-luciferase.

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Authors and Affiliations

  1. School of Molecular Biosciences, Washington State University, Pullman, WA, USA

    Y Zhang, Z Wang & N S Magnuson

  2. Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID, USA

    X Li

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  1. Y Zhang
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  2. Z Wang
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  3. X Li
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  4. N S Magnuson
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Correspondence to N S Magnuson.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Zhang, Y., Wang, Z., Li, X. et al. Pim kinase-dependent inhibition of c-Myc degradation. Oncogene 27, 4809–4819 (2008). https://doi.org/10.1038/onc.2008.123

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