PP2A-Mediated Dephosphorylation of p107 Plays a Critical Role in Chondrocyte Cell Cycle Arrest by FGF
2008

Role of PP2A in Chondrocyte Cell Cycle Arrest by FGF

publication Evidence: moderate

Author Information

Author(s): Victoria Kolupaeva, Emmanuel Laplantine, Claudio Basilico

Primary Institution: New York University School of Medicine

Hypothesis

Does p107 dephosphorylation play a critical role in the chondrocyte response to FGF?

Conclusion

p107 dephosphorylation is a key event in FGF-induced cell cycle arrest in chondrocytes, mediated by the PP2A phosphatase.

Supporting Evidence

  • FGF signaling inhibits chondrocyte proliferation.
  • p107 dephosphorylation is one of the earliest events in FGF-induced growth arrest.
  • Overexpression of cyclin D1/cdk4 prevents p107 dephosphorylation and growth arrest.
  • PP2A is activated by FGF to promote p107 dephosphorylation.
  • Inhibition of PP2A prevents FGF-induced p107 dephosphorylation.
  • Knockdown of PP2A delays p107 dephosphorylation and allows continued cell cycle progression.

Takeaway

When chondrocytes are treated with FGF, a protein called p107 gets changed in a way that stops the cells from growing. This change is helped by another protein called PP2A.

Methodology

The study involved overexpressing cyclin D1/cdk4 in RCS chondrocytes and analyzing the effects on p107 dephosphorylation and cell cycle arrest.

Limitations

The study did not isolate pure populations of cells with reduced levels of PP2A due to lethality of PP2A knockdown.

Digital Object Identifier (DOI)

10.1371/journal.pone.0003447

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