Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Biochem Biophys Res Commun. 2011 Mar 18;406(3):430-4. doi: 10.1016/j.bbrc.2011.02.062. Epub 2011 Feb 15.
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 3h in leukemic NB4, 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.
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）处理可以在 caspase-3 激活之前的 3 小时内降低白血病 NB4、Kasumi-1 和 Jurkat 细胞中全长 Ikaros（IK1）蛋白的表达。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。用蛋白酶体抑制剂 MG132 或环氧酶抑制剂 epoxomicin 处理，但不用钙蛋白酶抑制剂 calpeptin 处理，可以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的 NB4 细胞凋亡，表现为 Annexin V 阳性细胞的增加和 caspase 3 的更早激活。据我们所知，这是第一个报道表明，在化疗药物或 UV 处理后，IK1 可以在凋亡诱导的早期通过蛋白酶体系统降解。这些数据可能为 IK1 在凋亡中的作用和 IK1 的翻译后调控提供新的见解。
