Requirement for pre-existing of p21 to prevent doxorubicin-induced apoptosis through inhibition of caspase-3 activation
Requirement for pre-existing of p21 to prevent doxorubicin-induced apoptosis through inhibition of caspase-3 activation
复制标题
DOI：
10.1007/s11010-006-9206-7
复制
发表时间：
2006-10-01
影响因子：
4.3
通讯作者：
Lu, Y. J.
中科院分区：
文献类型：
--
作者：
Tang, J. J.;Shen, C.;Lu, Y. J.
细胞周期蛋白依赖性激酶(CDK)抑制剂p21(waf1/cip1/sdi1)抑制阿霉素(DOX)诱导的细胞凋亡。在这里，我们发现在DOX治疗之前，而不是在DOX治疗之后，p21的外源表达可以保护p21缺陷的人结直肠癌细胞DLD1免受DOX诱导的细胞凋亡。在以前的工作中，我们证明了p21通过其CDK结合和CDK抑制活性来抑制DOX诱导的细胞凋亡。在这里，我们报告了预先存在的p21可以与前caspase-3结合并抑制细胞中caspase-3的激活，这至少在一定程度上是提高DOX处理的细胞存活的原因。此外，在DLD1细胞中发现p21的N-末端结构域与原caspase-3相互作用。因此，我们认为需要预先存在的p21来防止DOX诱导的细胞凋亡。
Doxorubicin (DOX)-induced apoptosis is suppressed by p21 (waf1/cip1/sdi1), a cyclin dependent kinase (CDK) inhibitor. Here we show that exogenous expression of p21 before, but not after, the DOX-treatment protected p21-deficient human colorectal cancer cell line DLD1 from DOX-induced apoptosis. In previous work, we demonstrated that p21 inhibits DOX-induced apoptosis via its CDK-binding and CDK-inhibitory activity. Here we report that pre-existing p21 can associate with pro-caspase-3 and inhibit caspase-3 activation in the cells, which was at least in part responsible for enhancing survival of DOX-treated cells. Furthermore, the N-terminal domain of p21 was found to interact with pro-caspase-3 in DLD1 cells. Thus, we propose that pre-existing p21 is required to prevent DOX-induced apoptosis.