Caspase-3 regulates cell cycle in B cells: a consequence of substrate specificity

被引：150

作者：

Woo, M

Hakem, R

Furlonger, C

Hakem, A

Duncan, GS

Sasaki, T

Bouchard, D

Lu, LW

Wu, GE

Paige, CJ

Mak, TW ^{[1
]}

机构：

[1] Adv Med Discovery Inst, Toronto, ON M5G 2C1, Canada

[2] Ontario Canc Inst, Toronto, ON M5G 2N9, Canada

[3] Univ Toronto, St Michaels Hosp, Dept Med, Toronto, ON M2C 2T2, Canada

[4] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2N9, Canada

[5] Univ Toronto, Dept Immunol, Toronto, ON M5G 2N9, Canada

来源：

NATURE IMMUNOLOGY | 2003年 / 4卷 / 10期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1038/ni976

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1016 / 1022

页数：7

共 43 条

[31]

Ray RJ, 1998, J IMMUNOL, V160, P5886

[32] Essential role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity [J].