Mitogenic signalling and the p16INK4a–Rb pathway cooperate to enforce irreversible cellular senescence

@article{Takahashi2006MitogenicSA,
  title={Mitogenic signalling and the p16INK4a–Rb pathway cooperate to enforce irreversible cellular senescence},
  author={Akiko Takahashi and Naoko Ohtani and Kimi Yamakoshi and S Iida and Hidetoshi Tahara and Keiko Nakayama and Keiichi I. Nakayama and Toshinori Ide and Hideyuki Saya and Eiji Hara},
  journal={Nature Cell Biology},
  year={2006},
  volume={8},
  pages={1291-1297}
}
The p16INK4a cyclin-dependent kinase inhibitor has a key role in establishing stable G1 cell-cycle arrest through activating the retinoblastoma (Rb) tumour suppressor protein pRb in cellular senescence. Here, we show that the p16INK4a /Rb-pathway also cooperates with mitogenic signals to induce elevated intracellular levels of reactive oxygen species (ROS), thereby activating protein kinase Cδ (PKCδ) in human senescent cells. Importantly, once activated by ROS, PKCδ promotes further generation… Expand
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