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Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation

Oncogene volume 30, pages 4864–4873 (2011)Cite this article

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Abstract

Pdcd4 is a novel tumor suppressor protein that functions in the nucleus and the cytoplasm, and appears to be involved in the regulation of transcription and translation. In the cytoplasm, Pdcd4 has been implicated in the suppression of translation of mRNAs containing structured 5′-untranslated regions; however, the mechanisms that recruit Pdcd4 to specific target mRNAs and the identities of these mRNAs are mostly unknown. In this study, we have identified c-myb mRNA as the first natural translational target mRNA of Pdcd4. We have found that translational suppression of c-myb mRNA by Pdcd4 is dependent on sequences located within the c-myb-coding region. Furthermore, we have found that the N-terminal domain of Pdcd4 has an important role in targeting Pdcd4 to c-myb RNA by mediating preferential RNA binding to the Pdcd4-responsive region of c-myb mRNA. Overall, our work demonstrates for the first time that Pdcd4 is directly involved in translational suppression of a natural mRNA and provides the first evidence for a key role of the RNA-binding domain in targeting Pdcd4 to a specific mRNA.

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Acknowledgements

We thank M Hentze and D Ostareck for providing plasmids. This work was supported by the Deutsche Krebshilfe (10–1716), the Wilhelm-Sander-Stiftung (2004.088.1) and the Wellcome Trust. PS and LW were supported by the Graduate School of Chemistry (GSC-MS) at the University of Münster.

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Authors and Affiliations

  1. Institute for Biochemistry, Westfälische-Wilhelms-Universität Münster, Münster, Germany

    P Singh, L Wedeken & K-H Klempnauer

  2. Department of Biochemistry, University of Leicester, Leicester, UK

    L C Waters & M D Carr

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  1. P Singh
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Correspondence to K-H Klempnauer.

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Singh, P., Wedeken, L., Waters, L. et al. Pdcd4 directly binds the coding region of c-myb mRNA and suppresses its translation. Oncogene 30, 4864–4873 (2011). https://doi.org/10.1038/onc.2011.202

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