Ikaros is degraded by proteasome-dependent mechanism in the early phase of apoptosis induction
Ikaros is degraded by proteasome-dependent mechanism in the early phase of apoptosis induction
复制标题
Ikaros 在细胞凋亡诱导的早期阶段通过蛋白酶体依赖性机制降解。
DOI：
10.1016/j.bbrc.2011.02.062
复制
发表时间：
2011-03-18
影响因子：
3.1
通讯作者：
Wu, Ying-Li
中科院分区：
文献类型：
--
作者：
He, Li-Cai;Xu, Han-Zhang;Wu, Ying-Li
Ikaros是一种重要的转录因子，参与造血细胞的发育和分化。在这项工作中，我们发现化疗药物或紫外线(UV)治疗可以在不到3h的时间内降低白血病NM全长Ikaros(IK1)蛋白的表达。Kasumi-1和Jurkat细胞，在caspase-3激活之前。依托泊苷处理不能改变IK1的mRNA水平，但可以缩短IK1的半衰期。与蛋白酶体抑制剂MG132或环氧米星共同处理可抑制依托泊苷诱导的Ikaros下调。过表达IK1可以加速依托泊苷诱导NB4细胞的凋亡，表现为Annexin V阳性细胞增多和caspase 3更早激活。据我们所知，这是首次报道在化疗药物或紫外线治疗下，IK1可以在诱导凋亡的早期通过蛋白酶体系统降解。这些数据可能对IK1在细胞凋亡中的作用以及IK1的翻译后调控提供新的见解。(C)2011 Elsevier Inc.保留所有权利。
Ikaros is an important transcription factor involved in the development and differentiation of hematopoietic cells. In this work, we found that chemotherapeutic drugs or ultraviolet radiation (UV) treatment could reduce the expression of full-length Ikaros (IK1) protein in less than 3 h in leukemic NM. Kasumi-1 and Jurkat cells, prior to the activation of caspase-3. Etoposide treatment could not alter the mRNA level of IK1 but it could shorten the half-life of IK1. Co-treatment with the proteasome inhibitor MG132 or epoxomicin but not calpain inhibitor calpeptin inhibited etoposide-induced Ikaros downregulation. Overexpression of IK1 could accelerate etoposide-induced apoptosis in NB4 cells, as evidenced by the increase of Annexin V positive cells and the more early activation of caspase 3. To our knowledge, this is the first report to show that upon chemotherapy drugs or UV treatment, IK1 could be degraded via the proteasome system in the early phase of apoptosis induction. These data might shed new insight on the role of IK1 in apoptosis and the post-translational regulation of IK1. (C) 2011 Elsevier Inc. All rights reserved.