Article
- The EMBO Journal (2004) 23, 3325 - 3335
- doi:10.1038/sj.emboj.7600335
Published online: 29 July 2004
Subject Categories:
MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation
Gretchen Poortinga1, Katherine M Hannan1, Hayley Snelling1, Carl R Walkley1,2, Anna Jenkins1, Kerith Sharkey1, Meaghan Wall1, Yves Brandenburger3, Manuela Palatsides1, Richard B Pearson1,4, Grant A McArthur1,2,5,6 and Ross D Hannan1,4,6
- Division of Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia
- Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia
- Fox Chase Cancer Center, Human Genetics Program, Philadelphia, PA, USA
- Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia
- Division of Haematology/Medical Oncology, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia
- These two authors contributed equally to this work
Correspondence to:
Grant A McArthur, Molecular Oncology Laboratory, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3002, Victoria, Australia. Tel.: +61 3 9656 1195; Fax: +61 3 9656 1411; E-mail: grant.mcarthur@petermac.org
Ross D Hannan, Growth Control Laboratory, Trescowthick Research Laboratories, Peter Mac Callum Cancer Centre, St Andrew's Place, east Melbourne 3002, Victoria, Australia. Tel.: +61 3 9656 1747; Fax: +61 3 9656 1411; E-mail: ross.hannan@petermac.org
Received 7 April 2004; Accepted 28 June 2004
Abstract
The regulation of cell mass (cell growth) is often tightly coupled to the cell division cycle (cell proliferation). Ribosome biogenesis and the control of rDNA transcription through RNA polymerase I are known to be critical determinants of cell growth. Here we show that granulocytic cells deficient in the c-MYC antagonist MAD1 display increased cell volume, rDNA transcription and protein synthesis. MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter. Using siRNA, UBF was shown to be required for c-MYC-induced rDNA transcription. These data demonstrate that MAD1 and c-MYC reciprocally regulate rDNA transcription, providing a mechanism for coordination of ribosome biogenesis and cell growth under conditions of sustained growth inhibition such as granulocyte differentiation.
Keywords:
- growth,
- MYC,
- MAD,
- RNA polymerase I,
- UBF
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