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Cell Cycle-Dependent Translocation of PRC1 on the Spindle by Kif4 Is Essential for Midzone Formation and Cytokinesis

Zhu, Changjun ; Jiang, Wei ; Ruoslahti, Erkki

Proceedings of the National Academy of Sciences - PNAS, 2005-01, Vol.102 (2), p.343-348 [Periódico revisado por pares]

United States: National Academy of Sciences

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  • Título:
    Cell Cycle-Dependent Translocation of PRC1 on the Spindle by Kif4 Is Essential for Midzone Formation and Cytokinesis
  • Autor: Zhu, Changjun ; Jiang, Wei ; Ruoslahti, Erkki
  • Assuntos: Anaphase ; Antibodies ; Biological Sciences ; Cell Cycle ; Cell Cycle Proteins - metabolism ; Cellular biology ; Cyclin-dependent kinases ; Cyclin-Dependent Kinases - physiology ; Cyclins ; Cytokinesis ; HeLa Cells ; Humans ; Kinesin - physiology ; Mitosis ; Mitotic spindle apparatus ; Phosphorylation ; Plasmids ; Protein Transport ; Proteins ; Spindle Apparatus - metabolism
  • É parte de: Proceedings of the National Academy of Sciences - PNAS, 2005-01, Vol.102 (2), p.343-348
  • Notas: ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-1
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    ObjectType-Article-1
    ObjectType-Feature-2
    Abbreviations: esiRNA, endoribonucleases RNase III-prepared short interfering RNA; MT, microtubule; EYFP, enhanced yellow fluorescent protein; ECFP, enhanced cyan fluorescent protein; Cdk, cyclin-dependent kinase.
    Author contributions: C.Z. and W.J. designed research, performed research, analyzed data, and wrote the paper.
    To whom correspondence should be addressed. E-mail: wjiang@burnham.org.
    Communicated by Erkki Ruoslahti, The Burnham Institute, La Jolla, CA, November 24, 2004
  • Descrição: The spindle midzone, a conspicuous network of antiparallel interdigitating nonkinetochore microtubules between separating chromosomes, plays a crucial role in regulating the initiation and completion of cytokinesis. In this study, we report the use of time-lapse microscopy and a human kinesin endoribonucleases RNase III-prepared short interfering RNA (esiRNA) library to identify Kif4 as a motor protein that translocates PRC1, a spindle midzone-associated cyclin-dependent kinase substrate protein, to the plus ends of interdigitating spindle microtubules during the metaphase-to-anaphase transition. We show that Kif4 binds to PRC1 through its "stalk plus tail" domains and Kif4 and PRC1 colocalize on the spindle midzone/midbody during anaphase and cytokinesis. Suppression of Kif4 expression by Kif4 esiRNA results in the inhibition of PRC1 translocation, a block of the midzone formation, and a failure of cytokinesis. PRC1 translocation and midzone formation can be restored, and the cytokinetic defects can be rescued in Kif4 esiRNA-treated cells by coexpression of Kif4 but not its motor dead mutant Kif4md. Furthermore, we show that cyclin-dependent kinase phosphorylation of PRC1 controls the timing of PRC1 translocation by Kif4. These results, in light of the crucial role of PRC1 in midzone formation, indicate that cell cycle-dependent translocation of PRC1 by Kif4 is essential for midzone formation and cytokinesis.
  • Editor: United States: National Academy of Sciences
  • Idioma: Inglês

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