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Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERK–JMJD3–p16INK4a signaling axis

Oncogene volume 31, pages 3287–3297 (2012)Cite this article

Abstract

The B-cell translocation gene 3 (BTG3) is a member of the antiproliferative BTG gene family and a downstream target of p53. BTG3 also binds and inhibits E2F1. Although it connects functionally two major growth-regulatory pathways, the physiological role of BTG3 remains largely uncharacterized. Here, we present evidence that loss of BTG3 in normal cells induced cellular senescence, which was correlated with enhanced ERK–AP1 signaling and elevated expression of the histone H3K27me3 demethylase JMJD3/KDM6B, leading to acute induction of p16INK4a. Importantly, we also found that BTG3 expression is specifically downregulated in prostate cancer, thus providing a physiological link with human cancers. Our data suggest that BTG3 may have a fail-safe role against tumorigenic progression.

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Acknowledgements

This work was supported by grants from the National Science Council of Taiwan and Academia Sinica to S-Y Shieh.

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Authors and Affiliations

  1. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    T-Y Lin, Y-C Cheng, H-C Yang & S-Y Shieh

  2. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

    Y-C Cheng

  3. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    W-C Lin, C-C Wang & P-L Lai

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  1. T-Y Lin
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Correspondence to S-Y Shieh.

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Lin, TY., Cheng, YC., Yang, HC. et al. Loss of the candidate tumor suppressor BTG3 triggers acute cellular senescence via the ERK–JMJD3–p16INK4a signaling axis. Oncogene 31, 3287–3297 (2012). https://doi.org/10.1038/onc.2011.491

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