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Sci. Signal., 21 December 2010
Vol. 3, Issue 153, p. ec388
[DOI: 10.1126/scisignal.3153ec388]


Cell Cycle Beyond the Greatwall

L. Bryan Ray

Science, Science Signaling, AAAS, Washington, DC 20005, USA

Protein phosphorylation and dephosphorylation provide a central mechanism that controls the eukaryotic cell division cycle and entry of cells into mitosis. A form of protein phosphatase 2A (PP2A) has an important role inhibiting phosphorylation-dependent activation of cyclin-dependent kinase 1 (CDK1) itself and also dephosphorylating substrates of the active CDK1 that promote mitosis. PP2A activity is inhibited when another protein kinase, known as Greatwall, is activated (see the Perspective by Virshup and Kaldis). Mochida et al. and Gharbi-Ayachi et al. searched for substrates of Greatwall that might participate in the cell cycle regulatory machinery. When phosphorylated by Greatwall, a pair of small related proteins, Arpp19 and {alpha}-Endosulfine, inhibited activity of PP2A. These effects were critical for regulation of mitosis in Xenopus egg extracts and in human cancer cells. Greatwall itself is phosphorylated and activated by CDK1, thus apparently contributing to a feed-forward loop that contributes to the switchlike commitment of cells to mitosis.

S. Mochida, S. L. Maslen, M. Skehel, T. Hunt, Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis. Science 330, 1670–1673 (2010). [Abstract] [Full Text]

A. Gharbi-Ayachi, J.-C. Labbé, A. Burgess, S. Vigneron, J.-M. Strub, E. Brioudes, A. Van-Dorsselaer, A. Castro, T. Lorca, The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A. Science 330, 1673–1677 (2010). [Abstract] [Full Text]

D. M. Virshup, P. Kaldis, Enforcing the Greatwall in mitosis. Science 330, 1638–1639 (2010). [Abstract] [Full Text]

Citation: L. B. Ray, Beyond the Greatwall. Sci. Signal. 3, ec388 (2010).

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