AKT signalling is required for ribosomal RNA synthesis and progression of E mu-Myc B-cell lymphoma in vivo

Jennifer R Devlin; Katherine M Hannan; Pui Y Ng; Megan J Bywater; Jake Shortt; Carleen Cullinane; Grant A McArthur; Ricky W Johnstone; Ross D Hannan; Richard B Pearson

Journal article

AKT signalling is required for ribosomal RNA synthesis and progression of E mu-Myc B-cell lymphoma in vivo

Jennifer R Devlin, Katherine M Hannan, Pui Y Ng, Megan J Bywater, Jake Shortt, Carleen Cullinane, Grant A McArthur, Ricky W Johnstone, Ross D Hannan, Richard B Pearson

FEBS JOURNAL | WILEY-BLACKWELL | Published : 2013

DOI: 10.1111/febs.12135

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Abstract

The dysregulation of PI3K/AKT/mTORC1 signalling and/or hyperactivation of MYC are observed in a high proportion of human cancers, and together they form a 'super signalling' network mediating malignancy. A fundamental downstream action of this signalling network is up-regulation of ribosome biogenesis and subsequent alterations in the patterns of translation and increased protein synthesis, which are thought to be critical for AKT/MYC-driven oncogenesis. We have demonstrated that AKT and MYC cooperate to drive ribosomal DNA (rDNA) transcription and ribosome biogenesis, with AKT being essential for rDNA transcription and in vitro survival of lymphoma cells isolated from a MYC-driven model of ..

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University of Melbourne Researchers

Grant McArthur Author Melbourne Medical School

Jake Shortt Author The Sir Peter Maccallum Department of Oncology

Richard Pearson Author The Sir Peter Maccallum Department of Oncology

Ricky Johnstone Author The Sir Peter Maccallum Department of Oncology

Katherine Hannan Author Biochemistry and Pharmacology

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Grants

Awarded by National Health and Medical Research Council of Australia

Awarded by Merck

Funding Acknowledgements

We would like to thank Merck for supplying MK-2206. This work was supported by National Health and Medical Research Council of Australia project grants 1043884, 251608, 566702, 166908, 251688, 509087, 400116, 400120 and 566876. The researchers were funded by National Health and Medical Research Council of Australia fellowships (R. D. H., R. B. P. and R. W. J.), the Cancer Council of Victoria (Sir Edward Weary Dunlop Fellowship to G. A. M.) and the Leukaemia Foundation of Australia (PhD scholarship to J. R. D.). We thank Jeannette Schreuders, Susan Jackson and Rachael Walker for animal technical assistance.