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={A. Takahashi and N. Ohtani and Kimi Yamakoshi and S. Iida and H. Tahara and K. Nakayama and T. Ide and H. Saya and E. Hara},
  journal={Nature Cell Biology},
  year={2006},
  volume={8},
  pages={1291-1297}
}
  • A. Takahashi, N. Ohtani, +7 authors E. Hara
  • Published 2006
  • Medicine, Biology
  • Nature Cell Biology
  • 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… CONTINUE READING
    396 Citations

    Figures and Topics from this paper.

    Crosstalk between the Rb pathway and AKT signaling forms a quiescence-senescence switch.
    • 52
    • PDF
    Feedback between p21 and reactive oxygen production is necessary for cell senescence
    • 553
    • PDF
    Irreversibility of cellular senescence: dual roles of p16INK4a/Rb-pathway in cell cycle control
    • 54
    Cellular senescence and tumor suppressor gene p16
    • 347
    Parallel pathways in RAF-induced senescence and conditions for its reversion
    • 47
    • PDF
    Protein kinase D1 is essential for Ras-induced senescence and tumor suppression by regulating senescence-associated inflammation
    • P. Wang, L. Han, +8 authors J. Chen
    • Biology, Medicine
    • Proceedings of the National Academy of Sciences
    • 2014
    • 31
    • PDF
    Evidence for a CDK4-dependent checkpoint in a conditional model of cellular senescence
    • 8

    References

    SHOWING 1-10 OF 34 REFERENCES
    p16INK4a can initiate an autonomous senescence program
    • 145
    • PDF
    Reversal of human cellular senescence: roles of the p53 and p16 pathways
    • 1,027
    Ras Proteins Induce Senescence by Altering the Intracellular Levels of Reactive Oxygen Species*
    • 597
    • PDF
    Regulation of growth arrest in senescence: Telomere damage is not the end of the story
    • 156