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| The EMBO Journal
(1998) 17, 2728–2735, doi:10.1093/emboj/17.10.2728 |
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| Nuclear export of cyclin B1 and its possible role in the DNA damage-induced G2 checkpoint |
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| Fumiko Toyoshima, Tetsuo Moriguchi, Atsushi Wada, Makoto Fukuda and Eisuke Nishida |
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Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-oiwake, Sakyo-ku, Kyoto 606-01, Japan To whom correspondence should be addressed Eisuke Nishida, L50174@sakura.kudpc.kyoto-u.ac.jp Received 20 January 1998; Revised 16 March 1998; Accepted 16 March 1998. |
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| Abstract |
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| M-phase-promoting factor (MPF), a complex of cdc2 and a B-type cyclin, is a key regulator of the G2/M cell cycle transition. Cyclin B1 accumulates in the cytoplasm through S and G2 phases and translocates to the nucleus during prophase. We show here that cytoplasmic localization of cyclin B1 during interphase is directed by its nuclear export signal (NES)-dependent transport mechanism. Treatment of HeLa cells with leptomycin B (LMB), a specific inhibitor of the NES-dependent transport, resulted in nuclear accumulation of cyclin B1 in G2 phase. Disruption of an NES which has been identified in cyclin B1 here abolished the nuclear export of this protein, and consequently the NES-disrupted cyclin B1 when expressed in cells accumulated in the nucleus. Moreover, we show that expression of the NES-disrupted cyclin B1 or LMB treatment of the cells is able to override the DNA damage-induced G2 checkpoint when combined with caffeine treatment. These results suggest a role of nuclear exclusion of cyclin B1 in the DNA damage-induced G2 checkpoint. |
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| Keywords: cell cycle, cyclin, MPF, spatial control |
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