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Microtubule regulation in mitosis: tubulin phosphorylation by the cyclin-dependent kinase cdk1 □d (2005).
| Content Provider | CiteSeerX |
|---|---|
| Author | Fourest-Lieuvin, Anne Peris, Leticia Gache, Vincent Garcia-Saez, Isabel Juillan-Binard, Céline Lantez, Violaine |
| Abstract | The activation of the cyclin-dependent kinase Cdk1 at the transition from interphase to mitosis induces important changes in microtubule dynamics. Cdk1 phosphorylates a number of microtubule- or tubulin-binding proteins but, hitherto, tubulin itself has not been detected as a Cdk1 substrate. Here we show that Cdk1 phosphorylates �-tubulin both in vitro and in vivo. Phosphorylation occurs on Ser172 of �-tubulin, a site that is well conserved in evolution. Using a phosphopeptide antibody, we find that a fraction of the cell tubulin is phosphorylated during mitosis, and this tubulin phosphorylation is inhibited by the Cdk1 inhibitor roscovitine. In mitotic cells, phosphorylated tubulin is excluded from microtubules, being present in the soluble tubulin fraction. Consistent with this distribution in cells, the incorporation of Cdk1-phosphorylated tubulin into growing microtubules is impaired in vitro. Additionally, EGFP-�3-tubulin S172D/E mutants that mimic phosphorylated tubulin are unable to incorporate into microtubules when expressed in cells. Modeling shows that the presence of a phosphoserine at position 172 may impair both GTP binding to �-tubulin and interactions between tubulin dimers. These data indicate that phosphorylation of tubulin by Cdk1 could be involved in the regulation of microtubule dynamics during mitosis. |
| File Format | |
| Publisher Date | 2005-01-01 |
| Access Restriction | Open |
| Subject Keyword | Tubulin Phosphorylation Cyclin-dependent Kinase Cdk1 Microtubule Regulation Microtubule Dynamic Tubulin-binding Protein Cdk1 Inhibitor Roscovitine Cell Tubulin Gtp Binding S172d Mutant Soluble Tubulin Fraction Cdk1 Substrate Mitotic Cell Cdk1-phosphorylated Tubulin Tubulin Dimer Induces Important Change Phosphopeptide Antibody |
| Content Type | Text |
