Proteasome-dependent degradation of Chk1 kinase induced by the topoisomerase II inhibitor R16 contributes to its anticancer activity
文献类型：期刊论文
| 作者 | Feng, Jian-Ming; Zhu, Hong; Zhang, Xiao-Wei; Ding, Jian ; Miao, Ze-Hong
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| 刊名 | CANCER BIOLOGY & THERAPY
 |
| 出版日期 | 2008-11 |
| 卷号 | 7期号:11页码:1726-1731 |
| 关键词 | topoisomerase II inhibitor naphthalimide R16 colon carcinoma Chk1 proteasome anticancer activity |
| ISSN号 | 1538-4047 |
| DOI | 10.4161/cbt.7.11.6728 |
| 文献子类 | Article |
| 英文摘要 | The novel naphthalimide derivative R16 has been demonstrated to exhibit potent in vitro and in vivo anticancer activity by inhibiting topoisomerase II (Top2). R16 induces G(2) arrest via an ATM-activated Chk2-executed pathway, accompanied by reducing Chk1. In this study, R16 was demonstrated to trigger time and concentration-dependent Chk1 reduction which was unrelated to the mRNA level and HSP90-involved degradation. Pretreatment of HCT116 cells with the proteasome inhibitors MG132 or lactacystin prevented Chk1 decline induced by R16, accompanied by significant accumulation of ubiquitinated Chk1 protein, indicating the involvement of ubiquitin-proteasome pathway. Meanwhile, R16 also resulted in loss of Chk1 function. By site-specifically mutating the phosphorylation sites of Chk1 protein at Ser317 or at Ser345, we further demonstrated that R16-triggered Chk1 reduction was associated with its apoptotic induction and cell killing. In conclusion, the data reveal that the novel Top2 inhibitor R16 induces degradation of Chk1 via the ubiquitin-proteasome pathway, impairing the function of Chk1 and thus contributing to the anticancer activity of R16. |
| WOS关键词 | ADVANCED BREAST-CANCER ; ACETYLATOR PHENOTYPE ; CHECKPOINT KINASE-1 ; AMONAFIDE ; EXPRESSION ; PATHWAY ; PROTEIN ; STRESS |
| 资助项目 | National Natural Sciences Foundation of China[30772588] ; National Natural Sciences Foundation of China[30721005] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000261841700006 |
| 出版者 | TAYLOR & FRANCIS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279445]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Miao, Ze-Hong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Feng, Jian-Ming,Zhu, Hong,Zhang, Xiao-Wei,et al. Proteasome-dependent degradation of Chk1 kinase induced by the topoisomerase II inhibitor R16 contributes to its anticancer activity[J]. CANCER BIOLOGY & THERAPY,2008,7(11):1726-1731. |
| APA | Feng, Jian-Ming,Zhu, Hong,Zhang, Xiao-Wei,Ding, Jian,&Miao, Ze-Hong.(2008).Proteasome-dependent degradation of Chk1 kinase induced by the topoisomerase II inhibitor R16 contributes to its anticancer activity.CANCER BIOLOGY & THERAPY,7(11),1726-1731. |
| MLA | Feng, Jian-Ming,et al."Proteasome-dependent degradation of Chk1 kinase induced by the topoisomerase II inhibitor R16 contributes to its anticancer activity".CANCER BIOLOGY & THERAPY 7.11(2008):1726-1731. |
入库方式： OAI收割
来源：上海药物研究所
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