Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity.
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.
Mesh Terms:
Animals, Apoptosis, B-Lymphocytes, Bromodeoxyuridine, Caspase 3, Caspases, Cell Cycle, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases, Cyclins, Flow Cytometry, Immunohistochemistry, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Proliferating Cell Nuclear Antigen, Spleen, Substrate Specificity
Animals, Apoptosis, B-Lymphocytes, Bromodeoxyuridine, Caspase 3, Caspases, Cell Cycle, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases, Cyclins, Flow Cytometry, Immunohistochemistry, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Proliferating Cell Nuclear Antigen, Spleen, Substrate Specificity
Nat. Immunol.
Date: Oct. 01, 2003
PubMed ID: 12970760
View in: Pubmed Google Scholar
Download Curated Data For This Publication
119378
Switch View:
- Interactions 9