title: Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity.
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.
authors.affiliation: Ontario Cancer Institute, Toronto, Ontario M5G 2N9, Canada.
authors.forename: Minna
authors.initials: M
authors.lastname: Woo
authors.forename: Razqallah
authors.initials: R
authors.lastname: Hakem
authors.forename: Caren
authors.initials: C
authors.lastname: Furlonger
authors.forename: Anne
authors.initials: A
authors.lastname: Hakem
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Duncan
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Denis
authors.initials: D
authors.lastname: Bouchard
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Wu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Paige
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000276:immunology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000276:immunology / Q000378:metabolism; D016213:Cyclins / Q000096:biosynthesis / Q000276:immunology; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013379:Substrate Specificity
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D018844:Cyclin-Dependent Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D001973:Bromodeoxyuridine