Abstract
Caspases are important for apoptosis but are also involved in mammalian cell survival and cell division. Here we report that caspase-3 is a negative regulator of B cell cycling. Mice deficient in caspase-3 (Casp3−/− mice) have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation in vivo and hyperproliferation after mitogenic stimulation in vitro. Cdkn1a encodes p21 (also called Waf1 or Cip1), a cyclin-dependent kinase (CDK) inhibitor. Although expression of p21 was increased, CDK activities and proliferating cell nuclear antigen (PCNA) were increased in Casp3−/− B cells. Using Casp3−/−Cdkn1a−/− mice, we show that the hyperproliferation of Casp3−/− B cells is abolished when Cdkn1a is also deleted. Our genetic and biochemical data demonstrate that caspase-3 is essential in the regulation of B cell homeostasis.
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Acknowledgements
We thank M. Saunders for scientific editing and M. Eweida for technical assistance. Supported by Canadian Institutes of Health Research (to M.W.).
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Woo, M., Hakem, R., Furlonger, C. et al. Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity. Nat Immunol 4, 1016–1022 (2003). https://doi.org/10.1038/ni976
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DOI: https://doi.org/10.1038/ni976
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