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Article

  • The EMBO Journal (2007) 26, 3332 - 3345
  • doi:10.1038/sj.emboj.7601776

Published online: 28 June 2007



There is a Corrigendum (April 2009) associated with this Article.

Inhibition of c-Myc activity by ribosomal protein L11

Mu-Shui Dai1, Hugh Arnold2, Xiao-Xin Sun1, Rosalie Sears2 and Hua Lu1

  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

Correspondence to:

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

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.

  • Keywords:

    • cell cycle,
    • C-Myc,
    • L11,
    • ribosomal proteins,
    • transcription,
    • TRRAP