检索结果-南通市图书馆

Signaling control of the constitutive androstane receptor （CAR）

Protein & Cell 2014年第2期5卷 113-123页

作者： Hui Yang Hongbing Wang Department of Pharmaceutical Sciences University of Maryland School of Pharmacy 20 Penn Street Baltimore MD 21201 USA

The constitutive androstane receptor （CAR, NRll3） plays a crucial role in the regulation of drug metabolism, energy homeostasis, and cancer development through modulating the transcription of its numerous target genes. Different from prototypical nuclear receptors, CAR can be activated by either direct ligand binding or ligand-independent （indirect） mechanisms both initiated with nuclear translocation of CAR from the cytoplasm. In comparison to the well-defined ligand-based activation, indirect activation of CAR appears to be exclusively involved in the nuclear translocation through mecha- nisms yet to be fully understood. Accumulating evi- dence reveals that without activation, CAR forms a protein complex in the cytoplasm where it can be func- tionally affected by multiple signaling pathways. In this review, we discuss recent progresses in our under- standing of the signaling regulation of CAR nuclear accumulation and activation. We expect that this review will also provide greater insight into the similarity and difference between the mechanisms of direct vs. indirect human CAR activation.

关键词： constitutive androstane receptor nucleartranslocation phosphorylation signaling regulation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation

引用

Chinese Journal of Natural Medicines 2014年第3期12卷 186-193页

作者： ZHANG Xuan HUANG Sheng-Zhuo GU Wan-Gang YANG Liu-Meng CHEN Huan ZHENG Chang-Bo ZHAO You-Xing WAN David Chi-Cheong ZHENG Yong-Tang Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences&Yunnan Province KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common DiseasesKunming Institute of ZoologyChinese Academy of Sciences School of Pharmaceutical Science&Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical University Institute of Tropical Bioscience and Biotechnology Chinese Academy of Tropical Agricultural Sciences School of Biomedical Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research of Common DiseasesFaculty of MedicineThe Chinese University of Hong Kong School of Pharmacy China Pharmaceutical University

AIM： To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder （Thymelaeaceae）. METHOD： The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-time PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking. RESULTS： Wikstroelide M potently inhibited different HIV-1 strains, including HIV-lmn, HIV-1AI7, and HIV-19495, induced a cytopathic effect, with ECs0 values ranging from 3.81 to 15.65 ***-I. Wikstroelide M also had high inhibitory activities against HIV-2noD and HIV-2cBL_20-induced cytopathic effects with ECs0 values of 18.88 and 31.90 *** 1. The inhibitory activities of wikstroelide M on the three HIV-1 strains were further confirmed by p24 quantification assay, with ECs0 values ranging from 15.16 to 35.57 ***-1. Wikstroelide M also potently inhibited HIV-lnm induced cytolysis in MT-4 cells, with an ECs0 value of 9.60 *** ~. The mechanistic assay showed that wikstroelide M targeted HIV-I reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75. CONCLUSION： Wikslroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear Iranslocation through dismpting the interaction between integrase and LEDGF/p75.

关键词： Wikstroelide M Daphnane diterpene Daphne acutiloba Rehder HIV Reverse trascriptase integrase nucleartranslocation Lens epithelium-derived growth factor (LEDGF/p75) Molecular docking

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：