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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 gamma  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.

© 2003 by The American Society of Hematology.
 

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