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AP-1 complex is effector of Hox-induced cellular proliferation and transformation

Oncogene volume 19, pages 5134–5141 (2000)Cite this article

Abstract

Hox gene products, initially characterized as master regulators of embryonic patterning, are also required for proper functioning of adult tissues. There is also a growing body of evidence that links Hox proteins to regulation of cellular proliferation/transformation. However, the underlying molecular mechanisms of Hox-associated transformation and tissue growth have yet to be elucidated. Using a well established model system for studying changes in cellular proliferation induced by Hoxb4, we show that AP-1 activity is markedly increased in Hoxb4-transduced cells due to significant upregulation of Jun-B and Fra-1 protein levels. Furthermore, we also show that the specific changes in AP-1 protein expression are necessary for the proliferation effects induced by Hoxb4, and that these changes converge to increase levels of cyclin D1, a known integrator of proliferation signals. Our observations thus link Hox gene products with key elements of the cell cycle machinery.

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Acknowledgements

This work was supported by a grant (#10435) from the National Cancer Institute of Canada (to G Sauvageau). The authors acknowledge Drs Corey Largman for the generous gift of Hoxb4 antiserum, Dr Keith R Humphries for providing the MSCV PGK EGFP vector, Dr Kevin McBride for critical discussions regarding biochemistry of AP-1 complex, and Nadine Mayotte for technical support. The support of Nathalie Tessier, head of the Flow Cytometry Department of the IRCM, is also acknowledged. J Krosl is a recipient of American Society for Hematology Scholarship, and G Sauvageau is a MRC clinician scientist.

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Authors and Affiliations

  1. Laboratory of Molecular Genetics of Hemopoietic Stem Cells, Clinical Research Institute of Montréal, Montréal, H2W 1R7, Québec, Canada

    Jana Krosl & Guy Sauvageau

  2. Department of Medicine, Université de Montréal, Montréal, Québec, Canada

    Guy Sauvageau

  3. Division of Hematology, Hospital Maisonneuve-Rosemont, Université de Montréal, 2M4, Quebec, HIT, Canada

    Guy Sauvageau

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Krosl, J., Sauvageau, G. AP-1 complex is effector of Hox-induced cellular proliferation and transformation. Oncogene 19, 5134–5141 (2000). https://doi.org/10.1038/sj.onc.1203897

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