Modulation of Fos-mediated AP-1 transcription by the promyelocytic leukemia protein (original) (raw)

Oncogene volume 16, pages 2843–2853 (1998)Cite this article

Abstract

The growth and transformation suppressor function of promyelocytic leukemia (PML) protein are disrupted in acute promyelocytic leukemia (APL) as a result of its fusion to the **RAR**α gene by t(15;17) translocation. There is significant sequence homology between the dimerization domain of PML and the Fos family of proteins, which imply that PML may be involved in AP-1 activity. Here we show that PML can cooperate with Fos to stimulate its AP-1-mediated transcriptional activity. Cotransfection of PML with GAL4/Fos strongly induced Fos-mediated activation of GAL4-responsive reporters, indicating a functional interaction between Fos and PML in vivo. Deletion analysis of Fos and PML demonstrated that the intact C-terminal domain of Fos (containing the dimerization domain), and the RING-finger, B1 box and nuclear localization domains of PML are involved in the cooperative activity of Fos and PML. Immunoprecipitation and electrophoretic mobility shift assay showed that PML is associated with the AP-1 complex. PMLRARα was also found to enhance the transcriptional activity of GAL4/Fos. The addition of retinoic acid abrogated the PMLRARα, but not PML-induced stimulation of GAL4/Fos activity in a dose-dependent manner. This study demonstrated that PML is involved in the AP-1 complex and can modulate Fos-mediated transcriptional activity, which may contribute to its growth suppressor function.

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Authors and Affiliations

  1. Division of Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, Texas, USA
    Sadeq Vallian & Kun-Sang Chang
  2. Department of Molecular Medicine, King's College School of Medicine and Dentistry, London, SE5 9NU, UK
    Joop A Gäken, Elliot B Gingold & Farzin Farzaneh
  3. Wellcome/CRC Institute, University of Cambridge, Cambridge, CB2 1QR, UK
    Tony Kouzarides

Authors

  1. Sadeq Vallian
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  2. Joop A Gäken
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  3. Elliot B Gingold
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  4. Tony Kouzarides
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  5. Kun-Sang Chang
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  6. Farzin Farzaneh
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Vallian, S., Gäken, J., Gingold, E. et al. Modulation of Fos-mediated AP-1 transcription by the promyelocytic leukemia protein.Oncogene 16, 2843–2853 (1998). https://doi.org/10.1038/sj.onc.1201837

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