Woo Minna, Hakem Razqallah, Furlonger Caren, Hakem Anne, Duncan Gordon S, Sasaki Takehiko, Bouchard Denis, Lu Liwei, Wu Gillian E, Paige Christopher J, Mak Tak W
Ontario Cancer Institute, Toronto, Ontario M5G 2N9, Canada.
Nat Immunol. 2003 Oct;4(10):1016-22. doi: 10.1038/ni976. Epub 2003 Sep 14.
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.
半胱天冬酶对于细胞凋亡很重要，但也参与哺乳动物细胞的存活和细胞分裂。在此我们报告，半胱天冬酶-3是B细胞周期的负调节因子。缺乏半胱天冬酶-3的小鼠（Casp3-/-小鼠）脾脏B细胞数量增加，这些B细胞显示正常的细胞凋亡，但在体内增殖增强，在体外有丝分裂原刺激后过度增殖。Cdkn1a编码p21（也称为Waf1或Cip1），一种细胞周期蛋白依赖性激酶（CDK）抑制剂。尽管p21的表达增加，但Casp3-/- B细胞中的CDK活性和增殖细胞核抗原（PCNA）增加。使用Casp3-/-Cdkn1a-/-小鼠，我们表明当Cdkn1a也被删除时，Casp3-/- B细胞的过度增殖被消除。我们的遗传和生化数据表明，半胱天冬酶-3在B细胞稳态调节中至关重要。
