Entry into mitosis in vertebrate cells is guarded by a checkpoint that can be activated by a variety of insults, including chromosomal damage and disrupting microtubules (Rieder, C.L., and R.W. Cole. 1998. J. Cell Biol. 142:1013–1022; Rieder, C.L., and R.W. Cole. 2000. Curr. Biol. 10:1067–1070). This checkpoint acts at the end of interphase to delay cells from entering mitosis, causing cells in prophase to decondense their chromosomes and return to G2 phase. Here, we show that in response to microtubule poisons this “antephase” checkpoint is primarily mediated by the p38 stress kinases and requires the Chfr protein that is absent or inactive in several transformed cell lines (Scolnick, D.M., and T.D. Halazonetis. 2000. Nature. 406:430–435) and lung tumors (Mizuno, K., H. Osada, H. Konishi, Y. Tatematsu, Y. Yatabe, T. Mitsudomi, Y. Fujii, and T. Takahashi. 2002. Oncogene. 21:2328–2333). Furthermore, in contrast to previous reports, we find that the checkpoint requires ubiquitylation but not proteasome activity, which is in agreement with the recent demonstration that Chfr conjugates ubiquitin through lysine 63 and not lysine 48 (Bothos, J., M.K. Summers, M. Venere, D.M. Scolnick, and T.D. Halazonetis. 2003. Oncogene. 22:7101–7107).
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16 August 2004
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August 09 2004
Chfr acts with the p38 stress kinases to block entry to mitosis in mammalian cells
Takahiro Matsusaka,
Takahiro Matsusaka
Wellcome/Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Cambridge CB2 1QR, England, UK
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Jonathon Pines
Jonathon Pines
Wellcome/Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Cambridge CB2 1QR, England, UK
Search for other works by this author on:
Takahiro Matsusaka
Wellcome/Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Cambridge CB2 1QR, England, UK
Jonathon Pines
Wellcome/Cancer Research UK Gurdon Institute, and Department of Zoology, University of Cambridge, Cambridge CB2 1QR, England, UK
Address correspondence to J. Pines, Wellcome/Cancer Research UK Gurdon Institute, and Dept. of Zoology, Tennis Court Rd., University of Cambridge, Cambridge CB2 1QR, England, UK. Tel: 1223 334096. Fax: 1223 334089. email: [email protected]
Received:
January 28 2004
Accepted:
July 06 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 166 (4): 507–516.
Article history
Received:
January 28 2004
Accepted:
July 06 2004
Citation
Takahiro Matsusaka, Jonathon Pines; Chfr acts with the p38 stress kinases to block entry to mitosis in mammalian cells . J Cell Biol 16 August 2004; 166 (4): 507–516. doi: https://doi.org/10.1083/jcb.200401139
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