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Polycomb CBX7 has a unifying role in cellular lifespan

Nature Cell Biology volume 6, pages 67–72 (2004)Cite this article

An Author Correction to this article was published on 08 August 2022

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Abstract

In contrast to cancer cells and embryonic stem cells, the lifespan of primary human cells is finite. After a defined number of population doublings, cells enter in an irreversible growth-arrested state termed replicative senescence1. Mutations of genes involved in immortalization can contribute to cancer2,3. In a genetic screen for cDNAs bypassing replicative senescence of normal human prostate epithelial cells (HPrEC), we identified CBX7, a gene that encodes a Polycomb protein, as shown by sequence homology, its interaction with Ring1 and its localization to nuclear Polycomb bodies. CBX7 extends the lifespan of a wide range of normal human cells and immortalizes mouse fibroblasts by downregulating expression of the Ink4a/Arf locus. CBX7 does not inter-function or colocalize with Bmi1, and both can exert their actions independently of each other as shown by reverse genetics. CBX7 expression is downregulated during replicative senescence and its ablation by short-hairpin RNA (shRNA) treatment inhibited growth of normal cells though induction of the Ink4a/Arf locus. Taken together, these data show that CBX7 controls cellular lifespan through regulation of both the p16Ink4a/Rb and the Arf/p53 pathways.

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Figure 1: CBX7 extends cellular lifespan.
Figure 2: CBX7 is a polycomb protein.
Figure 3: CBX7 downregulates transcription of the Ink4a-Arf locus.
Figure 4: CBX7 is required for growth of normal cells.

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Acknowledgements

We thank W. Bordogna, M. van Lohuizen, F. Fuks, D. Wotton and P. Freemont for materials, M. Serrano, A. Carnero, M. Collado and all members of D. Beach's laboratory for thoughtful comments, and P. Gómez-Puertas for help with bioinformatic analysis. This work was supported by grants from Cancer Research UK, The Wellcome Trust, and the Hugh and Catherine Stevens Fund. J.G. is recipient of a Long Term Fellowship from the Human Frontier Science Program.

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Author notes

  1. Jesús Gil

    Present address: Molecular Oncology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

  2. David Bernard

    Present address: Free University of Brussels, Laboratory of Molecular Virology, Faculty of Medicine, Brussels, NULL 1070, Belgium

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  1. Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK

    Jesús Gil, David Bernard, Dolores Martínez & David Beach

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Correspondence to Jesús Gil.

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Gil, J., Bernard, D., Martínez, D. et al. Polycomb CBX7 has a unifying role in cellular lifespan. Nat Cell Biol 6, 67–72 (2004). https://doi.org/10.1038/ncb1077

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