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Identification of a novel centrosome/microtubule-associated coiled-coil protein involved in cell-cycle progression and spindle organization

Oncogene volume 24, pages 1159–1173 (2005)Cite this article

Abstract

Here we describe the identification of a novel vertebrate-specific centrosome/spindle pole-associated protein (CSPP) involved in cell-cycle regulation. The protein is predicted to have a tripartite domain structure, where the N- and C-terminal domains are linked through a coiled-coil mid-domain. Experimental analysis of the identified domains revealed that spindle association is dependent on the N-terminal and the coiled-coil mid domain. The expression of CSPP at the mRNA level was detected in all tested cell lines and in testis tissue. Ectopic expression of CSPP in HEK293T cells blocked cell-cycle progression in early G1 phase and in mitosis in a dose-dependent manner. Interestingly, mitosis-arrested cells contained aberrant spindles and showed impairment of chromosome congression. Inhibition of CSPP gene expression by small interfering RNAs induced cell-cycle arrest/delay in S phase. This phenotype was characterized by elevated levels of cyclin A, decreased levels of cyclin E and hyperphosphorylation of the S-phase checkpoint kinase Chk1. The activation of Chk1 may indicate a replication stress response due to an inappropriate G1/S-phase transition. Taken together, we demonstrate that CSPP is associated with centrosomes and microtubules and may play a role in the regulation of G1/S-phase progression and spindle assembly.

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Acknowledgements

We are thankful to K Solberg-Landsverk and M Strand for excellent assistance with the flow cytometry, Dr H Steen for help on the AX-70 microscope, and Drs S Funderud and E Boye for critical reading of the manuscript. The Norwegian Cancer Society and The Norwegian Research Council supported this work.

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Authors and Affiliations

  1. Department of Immunology, The Norwegian Radium Hospital, Montebello, 0310, Oslo, Norway

    Sebastian Patzke, Helena Hauge, Mouldy Sioud, Eivind Farmen Finne, Einar Andreas Sivertsen & Hans-Christian Aasheim

  2. Department of Pathology, The Norwegian Radium Hospital, Montebello, 0310, Oslo, Norway

    Jan Delabie

  3. Department of Radiation Biology, The Norwegian Radium Hospital, Montebello, 0310, Oslo, Norway

    Trond Stokke

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  1. Sebastian Patzke
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Correspondence to Hans-Christian Aasheim.

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Patzke, S., Hauge, H., Sioud, M. et al. Identification of a novel centrosome/microtubule-associated coiled-coil protein involved in cell-cycle progression and spindle organization. Oncogene 24, 1159–1173 (2005). https://doi.org/10.1038/sj.onc.1208267

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