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Sci. STKE, 14 October 2003
Vol. 2003, Issue 204, p. tw401
[DOI: 10.1126/stke.2003.204.tw401]

EDITORS' CHOICE

CELL CYCLE Caspases Inhibiting the Cell Cycle

Caspase 3 is best known for its role in programmed cell death or apoptosis. Woo et al. report that in Casp3–/–mice, there is hyperproliferation of mature B cells and that these cells are hyperresponsive to proliferative stimuli in vitro compared with B cells from Casp3 heterozygotes. Unlike activated T cells from these Casp3–/– mice, which hyperproliferate because of decreased apoptosis, the activated B cells show the same or slightly increased apoptosis compared with B cells from Casp3 heterozygotes. Casp3–/– B cells were impaired in ligand-mediated apoptosis (triggered by FasL), but not in apoptosis that derives from the intrinsic pathways (triggered by DNA damage). Compared with activated wild-type B cells, mitogen-stimulated Casp3–/– B cells exhibited increased levels of the cyclin-dependent kinase (CDK) inhibitor and PCNA (proliferating cell nuclear antigen)-associating protein p21. (The interaction of p21 with PCNA promotes cell cycle progression, whereas the interaction with CDKs inhibits cell cycle progression.) PCNA, p21, CDK2, and CDK4 were detected in a complex in the activated Casp3–/– B cells, but not in wild-type B cells. In double-knockout mice lacking both caspase 3 and p21, the hyperproliferative B cell response was abolished, whereas there was no effect on the T cell hyperproliferative response. Thus, p21 appears to be a selective substrate for caspase 3 that contributes to cell-type-specific control of the cell cycle.

M. Woo, R. Haken, C. Furlonger, A. Hakem, G. S. Duncan, T. Sasaki, D. Bouchard, L. Lu, G. E. Wu, G. J. Paige, T. W. Mak, Capsase-3 regulates cell cycle in B cells: A consequence of substrate specificity. Nat. Immunol. 4, 1016 -1022 (2003). [Full Text]

Citation: Caspases Inhibiting the Cell Cycle. Sci. STKE 2003, tw401 (2003).


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