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Prepublished online as a Blood First Edition Paper on November 7, 2002; DOI 10.1182/blood-2002-04-1103.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 1928-1933
NEOPLASIA
Nuclear localization of cyclin B1 regulates DNA damage-induced
apoptosis
Lisa A. Porter,
I.
Howard Cukier, and
Jonathan M. Lee
From the Hamilton Regional Cancer Center, Hamilton, ON,
Canada; and Department of Pathology and Molecular
Medicine, McMaster University, Hamilton, ON, Canada.
Some cells undergo apoptosis in response to DNA damage, whereas
others do not. To understand the biochemical pathways controlling this
differential response, we have studied the intracellular localization
of cyclin B1 in cell types sensitive or resistant to apoptosis induced
by DNA damage. We found that cyclin B1 protein accumulates in the
nucleus of cells that are sensitive to radiation-induced apoptosis
(thymocytes, lymphoid cell lines), but remains cytoplasmic in
apoptosis-resistant cells (primary and transformed fibroblasts). Treatment of both cell types with leptomycin B, an inhibitor of CRM1-dependent cyclin B1 nuclear export, induces apoptosis.
Furthermore, ectopic expression of cyclin B1-5xE, a protein
that preferentially localizes to the nucleus, is sufficient to trigger
apoptosis. Conversely, expression of cyclin B1-5xA, a
predominantly cytoplasmic protein, fails to induce apoptosis. This
suggests that nuclear accumulation is necessary for cyclin
B1-dependent apoptosis. Our observations are consistent with the idea
that localization of cyclin B1 is among the factors determining the
cellular decision to undergo apoptosis in response to DNA damage.

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