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dc.contributor.authorKang, J
dc.contributor.authorKusnadi, EP
dc.contributor.authorOgden, AJ
dc.contributor.authorHicks, RJ
dc.contributor.authorBammert, L
dc.contributor.authorKutay, U
dc.contributor.authorHung, S
dc.contributor.authorSanij, E
dc.contributor.authorHannan, RD
dc.contributor.authorHannan, KM
dc.contributor.authorPearson, RB
dc.date.accessioned2021-02-05T00:22:41Z
dc.date.available2021-02-05T00:22:41Z
dc.date.issued2016-08-02
dc.identifierpii: 10346
dc.identifier.citationKang, J., Kusnadi, E. P., Ogden, A. J., Hicks, R. J., Bammert, L., Kutay, U., Hung, S., Sanij, E., Hannan, R. D., Hannan, K. M. & Pearson, R. B. (2016). Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription. ONCOTARGET, 7 (31), pp.48887-48904. https://doi.org/10.18632/oncotarget.10346.
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/11343/259980
dc.description.abstractDysregulation 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 acids modulate growth factor-dependent rDNA transcription by primarily regulating S6K1-dependent rDNA transcription elongation and processing. Thus, we show for the first time amino acids regulate rRNA synthesis by a distinct, post-initiation mechanism, providing a novel model for integrated control of ribosome biogenesis that has implications for understanding how this process is dysregulated in cancer.
dc.languageEnglish
dc.publisherIMPACT JOURNALS LLC
dc.titleAmino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription
dc.typeJournal Article
dc.identifier.doi10.18632/oncotarget.10346
melbourne.affiliation.departmentSir Peter MacCallum Department of Oncology
melbourne.affiliation.departmentMedicine and Radiology
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.departmentOphthalmology (Eye & Ear Hospital)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleOncotarget
melbourne.source.volume7
melbourne.source.issue31
melbourne.source.pages48887-48904
melbourne.identifier.nhmrc509087
melbourne.identifier.nhmrc566876
melbourne.identifier.nhmrc1053792
melbourne.identifier.nhmrc566771
melbourne.identifier.nhmrc1003270
melbourne.identifier.nhmrc1038852
dc.rights.licenseCC BY
melbourne.elementsid1079340
melbourne.contributor.authorSanij, Elaine
melbourne.contributor.authorHannan, Ross
melbourne.contributor.authorPearson, Richard
melbourne.contributor.authorHannan, Katherine
melbourne.contributor.authorHicks, Rodney
melbourne.contributor.authorKusnadi, Eric
melbourne.contributor.authorHung, Sandy
melbourne.contributor.authorKusnadi, Eric
dc.identifier.eissn1949-2553
melbourne.identifier.fundernameidNHMRC, 509087
melbourne.identifier.fundernameidNHMRC, 566876
melbourne.identifier.fundernameidNHMRC, 1053792
melbourne.identifier.fundernameidNHMRC, 566771
melbourne.identifier.fundernameidNHMRC, 1003270
melbourne.identifier.fundernameidNHMRC, 1038852
melbourne.identifier.fundernameidCANCER COUNCIL VICTORIA, 1065118
melbourne.accessrightsOpen Access


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