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Inhibitor-2 induced M-phase arrest in Xenopus cycling egg extracts is dependent on MAPK activation


The evolutionarily-conserved protein phosphatase 1 (PP1) plays a central role in dephosphorylation of phosphoproteins during the M phase of the cell cycle. We demonstrate here that the PP1 inhibitor inhibitor-2 protein (Inh-2) induces an M-phase arrest in Xenopus cycling egg extracts. Interestingly, the characteristics of this M-phase arrest are similar to those of mitogen-activated protein kinase (p42MAPK)-induced M-phase arrest. This prompted us to investigate whether Inh-2-induced M-phase arrest was dependent on activation of the p42MAPK pathway. We demonstrate here that MAPK activity is required for Inh-2-induced M-phase arrest, as inhibition of MAPK by PD98059 allowed cycling extracts to exit M phase, despite the presence of Inh-2. We next investigated whether Inh-2 phosphorylation by the MAPK pathway was required to induce an M-phase arrest. We discovered that while p90Rsk (a MAPK protein required for M-phase arrest) is able to phosphorylate Inh-2, this phosphorylation is not required for Inh-2 function. Overall, our results suggest a novel mechanism linking p42MAPK and PP1 pathways during M phase of the cell cycle.



chromosome condensation


cytostatic factor


differential interference contrast


dimethyl sulfoxide


ethylene glycolbis(succinic acid N-hydrosysuccinimide ester)




mitogenactivated protein kinase


MAPK/extracellular signal-regulated kinase kinase


nuclear envelope breakdown


protein kinase A


p90 ribosomal S6 kinase-1


spindle assembly checkpoint


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Correspondence to Arian Khandani.

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Khandani, A., Mohtashami, M. & Camirand, A. Inhibitor-2 induced M-phase arrest in Xenopus cycling egg extracts is dependent on MAPK activation. Cell Mol Biol Lett 16, 669 (2011).

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Key words

  • Inhibitor-2
  • PP-1 phosphatase
  • MAPK kinase
  • p90Rsk
  • M-phase arrest
  • Xenopus cycling egg extract