Journal article

Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription

Jian Kang, Eric P Kusnadi, Allison J Ogden, Rodney J Hicks, Lukas Bammert, Ulrike Kutay, Sandy Hung, Elaine Sanij, Ross D Hannan, Katherine M Hannan, Richard B Pearson

ONCOTARGET | IMPACT JOURNALS LLC | Published : 2016

Abstract

Dysregulation of RNA polymerase I (Pol I)-dependent ribosomal DNA (rDNA) transcription is a consistent feature of malignant transformation that can be targeted to treat cancer. Understanding how rDNA transcription is coupled to the availability of growth factors and nutrients will provide insight into how ribosome biogenesis is maintained in a tumour environment characterised by limiting nutrients. We demonstrate that modulation of rDNA transcription initiation, elongation and rRNA processing is an immediate, co-regulated response to altered amino acid abundance, dependent on both mTORC1 activation of S6K1 and MYC activity. Growth factors regulate rDNA transcription initiation while amino ac..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by Cancer Council Victoria


Awarded by Prostate Cancer Foundation of Australia


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) of Australia project and program grants (509087; 566876; 1044881; 1042890; 1053792; 566771; 1003270; 1038852), Cancer Council Victoria (1065118); Prostate Cancer Foundation of Australia (CG1511); Leukaemia Foundation, and Captain Courageous Foundation (ADBA #1). Researchers are funded by NHMRC Fellowships (R.D.H and R.B.P), the postgraduate scholarships from the University of Melbourne and Cancer Therapeutics CRC (E.P.K), and the Swiss National Science Foundation in the framework of the NCCR 'RNA and disease' (U.K).