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Point of no return for senescence

Senescent cells live on but can never again divide. This proliferative block is thought to safeguard against rampant oncogenic cell division. Akiko Takahashi, Eiji Hara, and colleagues (University of Tokushima, Japan) now show that, to enforce this irreversible stasis, cells switch on a self-perpetuating loop that suppresses cytokinesis.

Stable cell cycle arrest is induced by activating the retinoblastoma (RB) tumor suppressor. In senescent human cells, unlike nonsenescent cells, subsequent inactivation of RB leads to the reinitiation of DNA replication but no proliferation, suggesting that a second safety mechanism arrests senescent cells in G2 or M phase.

This second arrest only works in cells that are grown in mitogen-rich (and thus tumor friendly) conditions, the authors now find. The mitogens induce reactive oxygen species (ROS), which then start a self-perpetuating loop. The team observed that ROS remained high in senescent cells even after RB inactivation.

ROS, which are thought to induce senescence, are known to activate PKC, which studies suggest in turn activates ROS production. Consistent with this positive feedback, levels of PKC were also high in the permanently arrested cells.

High PKC, the team showed, suppressed the WARTS cytokinesis activator. Inhibiting PKC released this suppression and enabled senescent cells that managed to escape the early RB-induced block to proliferate.

Reference:

Takahasi, A., et al. 2006. Nat. Cell Biol. doi:10.1038/ncb1491.

Ruth Williams

ruth.williams{at}rockefeller.edu

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This Article Full Text (PDF, 928K) Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Social Bookmarking                            What's this?