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| Subject Categories: Chromatin & Transcription |
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| The EMBO Journal
(2007) 26, 3332–3345, doi:10.1038/sj.emboj.7601776 Published online 28 June 2007 |
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| Inhibition of c-Myc activity by ribosomal protein L11 |
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| Mu-Shui Dai1, Hugh Arnold2, Xiao-Xin Sun1, Rosalie Sears2 and Hua Lu1 |
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1 Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, Portland, OR, USA 2 Department of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, OR, USA To whom correspondence should be addressed Hua Lu, Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Tel.: +1 503 494 7414; Fax: +1 503 494 8393; E-mail: luh@ohsu.edu Received 21 December 2006; Accepted 4 June 2007; Published online 28 June 2007. |
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| Abstract |
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| The c-Myc oncoprotein promotes cell growth by enhancing ribosomal biogenesis through upregulation of RNA polymerases I-, II-, and III-dependent transcription. Overexpression of c-Myc and aberrant ribosomal biogenesis leads to deregulated cell growth and tumorigenesis. Hence, c-Myc activity and ribosomal biogenesis must be regulated in cells. Here, we show that ribosomal protein L11, a component of the large subunit of the ribosome, controls c-Myc function through a negative feedback mechanism. L11 is transcriptionally induced by c-Myc, and overexpression of L11 inhibits c-Myc-induced transcription and cell proliferation. Conversely, reduction of endogenous L11 by siRNA increases these c-Myc activities. Mechanistically, L11 binds to the Myc box II (MB II), inhibits the recruitment of the coactivator TRRAP, and reduces histone H4 acetylation at c-Myc target gene promoters. In response to serum stimulation or serum starvation, L11 and TRRAP display inverse promoter-binding profiles. In addition, L11 regulates c-Myc levels. These results identify L11 as a feedback inhibitor of c-Myc and suggest a novel role for L11 in regulating c-Myc-enhanced ribosomal biogenesis. |
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| Keywords: cell cycle, C-Myc, L11, ribosomal proteins, transcription, TRRAP |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSThe Myc trilogy: lord of RNA polymerases Nature Cell Biology News and Views (01 Mar 2005) RESEARCHBOB.1/OBF.1 controls the balance of TH1 and TH2 immune responses The EMBO Journal Article (11 Jul 2007) Inhibition of c-Myc activity by ribosomal protein L11 The EMBO Journal Article c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription Nature Cell Biology Letter (01 Mar 2005) |
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