Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis
| Autor: | Shuh Narumiya, Kazuhiro Kimura, Tokuko Haraguchi, Yasushi Hiraoka, Chiharu Higashida, Shingo Yasuda, Toshio Kitamura, Fabian Oceguera-Yanez |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Prometaphase
Chromosomal Proteins Non-Histone Mitosis Cell Cycle Proteins Protamine Kinase Spindle Apparatus macromolecular substances Biology Transfection Autoantigens Article chemistry.chemical_compound Tubulin Proto-Oncogene Proteins Humans Kinetochores cdc42 GTP-Binding Protein Metaphase Research Articles RNA Double-Stranded Nocodazole Calcium-Binding Proteins Cell Cycle GTPase-Activating Proteins Cell Biology rac GTP-Binding Proteins Cell biology Spindle apparatus Repressor Proteins Rac GTP-Binding Proteins Kinetics Microscopy Fluorescence Cdc42 GTP-Binding Protein chemistry Mad2 Proteins Mutation RNA Interference biological phenomena cell phenomena and immunity Microtubule-Associated Proteins Centromere Protein A Cytokinesis HeLa Cells Thymidine |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200408085 |
| Popis: | Although Rho regulates cytokinesis, little was known about the functions in mitosis of Cdc42 and Rac. We recently suggested that Cdc42 works in metaphase by regulating bi-orient attachment of spindle microtubules to kinetochores. We now confirm the role of Cdc42 by RNA interference and identify the mechanisms for activation and down-regulation of Cdc42. Using a pull-down assay, we found that the level of GTP-Cdc42 elevates in metaphase, whereas the level of GTP-Rac does not change significantly in mitosis. Overexpression of dominant-negative mutants of Ect2 and MgcRacGAP, a Rho GTPase guanine nucleotide exchange factor and GTPase activating protein, respectively, or depletion of Ect2 by RNA interference suppresses this change of GTP-Cdc42 in mitosis. Depletion of Ect2 also impairs microtubule attachment to kinetochores and causes prometaphase delay and abnormal chromosomal segregation, as does depletion of Cdc42 or expression of the Ect2 and MgcRacGAP mutants. These results suggest that Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis. |
| Databáze: | OpenAIRE |
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