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

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

DOI: 10.18632/oncotarget.10346

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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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University of Melbourne Researchers

Eric Kusnadi Author The Sir Peter Maccallum Department of Oncology

Richard Pearson Author The Sir Peter Maccallum Department of Oncology

Rodney Hicks Author Medicine - St Vincent's Hospital

Elaine Sanij Author Medicine - St Vincent's Hospital

Sandy Hung Author Ophthalmology Eye and Ear Hospital

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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).