Letter abstract
Nature Cell Biology 6, 67 - 72 (2003)
Published online: 30 November 2003 | doi:10.1038/ncb1077
Polycomb CBX7 has a unifying role in cellular lifespan
Jesús Gil1,2, David Bernard1,3, Dolores Martínez1 & David Beach1
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.
- Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.
- Present address: Molecular Oncology Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
- Present address: Free University of Brussels, Laboratory of Molecular Virology, Faculty of Medicine, Brussels, NULL 1070, Belgium.
Correspondence to: Jesús Gil1,2 e-mail: jesus.gil@cancer.org.uk
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