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Identification of FUSE-binding protein 1 as a regulatory mRNA-binding protein that represses nucleophosmin translation

Abstract

Nucleophosmin (NPM/B23) is a multifunctional oncoprotein whose protein expression levels dictate cellular growth and proliferation rates. NPM is translationally responsive to hyperactive mammalian target of rapamycin (mTOR) signals, but the mechanism of this regulation is not understood. Using chimeric translational reporters, we found that the 3′ untranslated region (UTR) of the NPM messenger (m)RNA is sufficient to mediate its translational modulation by mTOR signalling. We show that far upstream element (FUSE)-binding protein 1 (FBP1) interacts specifically with the 3′ UTR of NPM to repress translation. Overexpression of FBP1 resulted in translational repression of NPM mRNAs, whereas depletion of FBP1 caused a dramatic increase in NPM translation and resulted in enhanced overall cell proliferation. Thus, we propose that FBP1 is a key regulator of cell growth and proliferation through its ability to selectively bind the NPM 3′ UTR and repress NPM translation.

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Acknowledgements

We thank the members of the Weber, Townsend and Piwnica-Worms laboratories for their advice and technical assistance. The luciferase reporter work was initiated through a Pilot Grant from the Washington University Imaging Center. MEO was supported by NIH 5T32 GM007067. This research was supported with Grants from the National Institutes of Health, P30 CA91842 to the Siteman Comprehensive Cancer Center and P41RR000954 and UL1 RR024992 from the National Center for Research Resources to the Proteomics Center. DPW and BLM were supported by NIH P50 CA94056. This work was supported by NIH Grant CA128007 and an Era of Hope Scholar Award in Breast Cancer Research (BC007304) to JDW.

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Correspondence to J D Weber.

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Olanich, M., Moss, B., Piwnica-Worms, D. et al. Identification of FUSE-binding protein 1 as a regulatory mRNA-binding protein that represses nucleophosmin translation. Oncogene 30, 77–86 (2011). https://doi.org/10.1038/onc.2010.404

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  • DOI: https://doi.org/10.1038/onc.2010.404

Keywords

  • FBP1
  • Nucleophosmin
  • ribosome biogenesis
  • translation

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