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The Rb-family protein p107 inhibits translation by a PDK1-dependent mechanism

Oncogene volume 21, pages 7891–7896 (2002)Cite this article

Abstract

The Rb family of proteins, which consists of Rb, p107 and p130, are critical regulators of cell proliferation. In addition to their inhibitory effects on cell cycle progression, Rb-family proteins repress transcription by RNA polymerases I and III, and may therefore restrain cell growth. However, it is not known if Rb, p107 or p130 have direct effects on protein synthesis. Here we report that ectopic expression of p107 in rat fibroblasts markedly attenuates the stimulation of mRNA translation and global protein synthesis by serum growth factors. This effect is associated with a reduction in the phosphorylation and activation of the serine-threonine kinases Akt1 and p70 S6 kinase (S6K1), two downstream targets of phosphoinositide-dependent kinase 1 (PDK1). We show that overexpression of p107 interferes with the recruitment of PDK1 to the plasma membrane in response to growth factors. Overexpression of PDK1 restores the defect in translation elicited by p107. These results suggest that p107 restricts cell growth by interfering with the phosphoinositide 3-kinase (PI3K) signaling pathway.

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Acknowledgements

We thank M Ewen, B Hemmings, N Sonenberg, A Toker and L Zhu for reagents. We also thank C Charbonneau for help with confocal microscopy and imaging. This work was supported by grants from the Canadian Institutes for Health Research to S Meloche and the National Cancer Institute of Canada to DR Kaplan. L Voisin is a recipient of a fellowship from the Heart and Stroke Foundation of Canada. S Meloche is an Investigator of the Canadian Institutes for Health Research.

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Author notes

  1. Constantin Makris

    Present address: Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 92093, California, CA, USA

  2. Constantin Makris and Laure Voisin: These authors contributed equally to this work and are listed alphabetically

Authors and Affiliations

  1. Institut de recherches cliniques de Montréal and Department of Pharmacology, University of Montreal, 110 Pine Avenue West, Montreal, Quebec, H2W 1R7, Canada

    Constantin Makris, Laure Voisin, Edith Giasson & Sylvain Meloche

  2. Brain Tumor Research Center, Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, H3A 2B4, Canada

    Christopher Tudan & David R Kaplan

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  1. Constantin Makris
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Correspondence to Sylvain Meloche.

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Makris, C., Voisin, L., Giasson, E. et al. The Rb-family protein p107 inhibits translation by a PDK1-dependent mechanism. Oncogene 21, 7891–7896 (2002). https://doi.org/10.1038/sj.onc.1205964

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