检索结果-南通市图书馆

AXL receptor signalling suppresses p53 in melanoma through stabilization of the MDMX-MDM2 complex

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2017年第2期9卷 154-165页

作者： Anna de Polo Zhongling Luot Casimiro Gerarduzzi Xiang Chen John B. Little zhi-min yuan John B. Little Center for Radiation Sciences Harvard T.H. Chan School of Public Health Boston MA 02115 USA Department of Dermatology Xiangya Hospital Central South University Changsha 410008 China

Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, but its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the sta- biUty of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpres- sion or activation through growth arrest-specific 6 （Gas6） Ugand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity. Upon activation, AXL stabilizes MDMX through a post-translational modification that involves phosphoryl- ation of MDMX on the phosphosite Ser314, leading to increased affinity between MDMX and MDM2 and favouring MDMX nuclear translocation. Ser314 phosphorylation can also protect MDMX from MDM2-mediated degradation, leading to stabilization of the MDMX-MDM2 complex. We identified CDK4/6 and p38 MAPK as the two kinases mediating AXL-induced modulation of the MDMX-MDM2 complex, and demonstrated that suppression of AXL, either through siRNA silencing or pharmacological inhibition, increases expression levels of p53 target genes P21, MDM2, and PUMA, improves p53 pathway response to chemotherapy, and sensitizes cells to both Cisplatin and Vemurafenib. Our findings offer an insight into a novel signalling axis linking AXL to p53 and provide a potentially druggable pathway to restore p53 function in melanoma.

关键词： MDMX MDM2 AXL CDK4/6 p53 melanoma

MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2020年第9期12卷 713-722页

作者： Bing Wang Chuan-Bian Lim Jiawei Yan Lizhen Li Jufang Wang John B.Little zhi-min yuan Key Laboratory of Space Radiobiology of Gansu Province&Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences Institute of Modern PhysicsChinese Academy of SciencesLanzhouChina University of Chinese Academy of Sciences BeijingChina John B.Little Center for Radiation Sciences Harvard T.H.Chan School of Public HealthBostonMAUSA Present address:School of Life Sciences and Technology ShanghaiTech UniversityShanghaiChina

A role of tumor-suppressive activity of p53 in the tumor microenvironment(TME)has been implicated but remains fairly *** address this knowledge gap,we leveraged our MdmxS314A mice as recipients to investigate how implanted tumor cells incapacitate host p53 creating a conducive TME for tumor *** found that tumor cell-associated stress induced p53 downregulation in peritumor cells via an MDMX-Ser314 phosphorylation-dependent *** a result,an immunosuppressive TME was developed,as reflected by diminished immune cell infiltration into tumors and compromised macrophage M1 ***,ablation of MDMX-Ser314 phosphorylation attenuated p53 decline in peritumor cells,which was associated with mitigation of immunosuppression and significant tumor growth *** data collectively uncover a novel role of p53 in regulating the tumor immune microenvironment,suggesting that p53 restoration in the TME can be exploited as a potential strategy of anticancer therapy.

关键词： p53 MDMX tumor microenvironment immune cell infiltration macrophage polarization

ZBTB7A governs estrogen receptor alpha expression in breast cancer

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2018年第4期10卷 273-284页

作者： Mary Ellen Molloy Monika Lewinska Amanda K. Williamson Thanh Thao Nguyen Gamze Kuser-Abali Lu Gong Jiawei Yan John B. Little Pier Paolo Pandolfi zhi-min yuan Department of Environmental Health John B. Little Center for Radiation Sciences Harvard T.H. Chan School of Public Health Boston MA 02215 USA Biotech Research and Innovation Centre Department of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Cancer Genetics Program Beth Israel Deaconess Cancer Center Departments of Medicine and Pathology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 USA

ZBTB7A, a member of the POZ/BTB and Krüppel （POK） family of transcription factors, has been shown to have a context-dependent role in cancer development and progression. The role of ZBTB7A in estrogen receptor alpha （ERα）-positive breast cancer is largely unknown. Approximately 70% of breast cancers are classified as ERα-positive. ERα carries out the biological effects of estrogen and its expression level dictates response to endocrine therapies and prognosis for breast cancer patients. In this study, we find that ZBTB7A transcriptionally regulates ERα expression in ERα-positive breast cancer cell lines by binding to the ESR1 promoter leading to increased transcription of ERα. Inhibition of ZBTB7A in ERα-positive cells results in decreased estrogen responsiveness as demonstrated by diminished estrogen-response element-driven luciferase reporter activity, induction of estrogen target genes, and estrogen-stimulated growth. We also report that ERα potentiates ZBTB7A expression via a post-translational mechanism, suggesting the presence of a positive feedback loop between ZBTB7A and ERα, conferring sensitivity to estrogen in breast cancer. Clinically, we find that ZBTB7A and ERα are often co-expressed in breast cancers and that high ZBTB7A expression correlates with improved overall and relapse-free survival for breast cancer patients. Importantly, high ZBTB7A expression predicts a more favorable outcome for patients treated with endocrine therapies. Together, these findings demonstrate that ZBTB7A contributes to the transcriptional program maintaining ERα expression and potentially an endocrine therapy-responsive phenotype in breast cancer.

关键词： ZBTB7A ERα breast cancer endocrine therapies

分子长程作用导致的电子态转移半径典量子理论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

无机化学学报 1999年第3期15卷 324-330页

作者：张昀闵志元李重德南京大学化学化工学院

以半经典量子力学方法发展了一个广义的理论，用来描述分子间长程作用下碰撞导致的电子态跃迁过程。运用分子间特别是线性分子间的一级静电Ｈａｍｉｌｔｏｎｉａｎ推导碰撞导致的电子态跃迁矩阵元的表达式，分别考虑了共振和近共振两种... 详细信息

以半经典量子力学方法发展了一个广义的理论，用来描述分子间长程作用下碰撞导致的电子态跃迁过程。运用分子间特别是线性分子间的一级静电Ｈａｍｉｌｔｏｎｉａｎ推导碰撞导致的电子态跃迁矩阵元的表达式，分别考虑了共振和近共振两种能量转移的情形，获得了对应于电子和分子转动运动的选律。

关键词：分子间长程作用碰撞电子态跃迁能量转移

维普期刊数据库

不确定经济环境下基于EVA的鲁棒供应链网络设计模型

在线全文

学校读者我要写书评

暂无评论

控制与决策 2017年第2期32卷 203-212页

作者：邱若臻陈瑞颍关志民黄小原东北大学工商管理学院沈阳110004

针对由制造商、仓库、分销中心和客户组成的四级供应链网络设计问题,考虑以产品需求、短期利率、长期利率、无风险利率、预期市场回报、证券承销费用和市场流动性等因素描述的经济环境不确定性,建立以供应链经济增加值绩效为目标,网络... 详细信息

针对由制造商、仓库、分销中心和客户组成的四级供应链网络设计问题,考虑以产品需求、短期利率、长期利率、无风险利率、预期市场回报、证券承销费用和市场流动性等因素描述的经济环境不确定性,建立以供应链经济增加值绩效为目标,网络设计、物流和财务运作为约束条件,设施选择、连接路径等为网络要素,生产、运输等物流量和负债、保理、应收账款等财务项为决策变量的多产品、多周期供应链网络鲁棒设计模型.数值结果表明,基于经济增加值的鲁棒供应链网络能够有效应对经济不确定性的影响.特别地,与传统随机优化方法相比,鲁棒优化能够确保供应链网络具有更好的鲁棒性和财务状况.

关键词：供应链经济增加值鲁棒优化经济不确定网络设计

维普期刊数据库

Physical Layer Security Scheme With AoI-Awareness for Industrial IoT Based on Covert Communications

在线全文

学校读者我要写书评

暂无评论

IEEE/CAA Journal of Automatica Sinica 2025年第1期 276-278页

作者： Yaping Li zhi-Xin Liu Jia-Wei Su Ya-Zhou yuan the Key Laboratory of Industrial Computer Control Engineering of Hebei Province Yanshan University

Dear Editor,Industrial Internet of things(IIoT) is a typical application of cyberphysical system(CPS). In the IIoT, wireless communication is an inevitable trend to replace the deployment-limited wired transmission for cases with large-scale and mobile devices. However, wireless communication gives rise to critical issues related to physical security, such as malicious detections and attacks [1].

关键词：

Sesquiterpenoids,isolated from Commiphora opobalsamum,induce cell cycle arrest and inhibit androgen receptor transactivity in prostate cancer cells

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Sesquiterpenoids,isolated from Commiphora opobalsamum,induce...

辐射后A549细胞上清外泌体磷脂酰肌醇蛋白聚糖-1表达与细胞增殖的相关性

山东生物化学与分子生物学会2009年学术会议

作者： Wang Xiao-Ling,Kong Feng,Xu Ai-Hui,Hu zhi-min,yuan Hui-Qing~* Department of Biochemistry and Molecular Biology,School of Medicine,Shandong University, Jinan 250012,China

Eight sesquiterpenoids were isolated from the resinous exudates of Commiphora *** structures were established on the basis of physi-chemical properties, H-NMR and C-NMR *** effects of these compounds on cellular growth were examined in several cancer cell *** sesquiterpenoids,(1(10)E,2R,4R)-2-methoxy-8,12- epoxygermacra-1(10),7,11-trien-6-one(ST1),and 2-methoxy-5-acetoxy-furanogermacr-1(10)-en -6-one(ST2),were shown to inhibit effectively cell proliferation of the prostate cancer cell lines in a concerntration-dependent manner,while less cytotoxicity of these compounds was shown by using immortalizied liver normal cell line at concerntrations *** cycle analysis by flow cytometry showed that cells were arrested at the G1 phase after chemical *** analysis showed that the two sesquiterpenoids induced the expression of p21,and produced a reduction of cyclinD as well in prostate cancer ***-mediated cellular proliferation inhibition was associated with a decrease of AR expression at mRNA and protein levels,and decreased the AR translocation in ***,the functional biomarkers used in evaluation of AR transactivity showed suppressions of prostate-specific antigen promoterdependent and androgen responsive element-dependent luciferase ***,the state of interaction of the AR with ARA70 and SRC-1 treated by ST plus androgen was different from that by androgen treatment alone as demonstrated by coimmunoprecipitation experiments. Therefore,Anti-AR properties ascribed to sesquiterpenoids from myrrh suggested that sesquiterpenoid-containing drugs could be used for the development of novel therapeutic chemicals.

关键词： myrrh germacrane sesquiterpenoids cell cycle androgen receptor prostate carcinoma cell lines

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

中国生物制品学杂志 2017年第9期30卷 912-916页

作者：王溪贾硕佟志敏胡媛媛金鹏张红梅吉林大学第二医院放疗科吉林长春130021 中南大学湘雅医学院附属湘雅二医院湖南长沙410011 吉林省申邦细胞工程研究所吉林长春130000 吉林大学中日联谊医院吉林长春130000

目的观察辐射后肺腺癌A549细胞的增殖情况,探讨其与细胞上清外泌体中磷脂酰肌醇蛋白聚糖-1表达的相关性。方法培养肺腺癌A549细胞,分别给予0、0.5、1.0、1.5、2.0 Gy剂量(剂量率1.75 Gy/time,300 Mu/min)辐射,辐射后培养6、12 h。采用C... 详细信息

目的观察辐射后肺腺癌A549细胞的增殖情况,探讨其与细胞上清外泌体中磷脂酰肌醇蛋白聚糖-1表达的相关性。方法培养肺腺癌A549细胞,分别给予0、0.5、1.0、1.5、2.0 Gy剂量(剂量率1.75 Gy/time,300 Mu/min)辐射,辐射后培养6、12 h。采用CCK8法检测细胞增殖情况,收集细胞上清液,超速离心法提取外泌体,Western blot法检测外泌体膜蛋白GPC1的表达情况。结果辐射后A549细胞增殖能力减弱,与0 Gy组相比,各剂量组A450均减小,且随辐射剂量的增加,A450越来越小;各剂量组上清外泌体GPC1蛋白表达均减少(P<0.001)。结论放疗可抑制A549细胞的增殖,且随辐射剂量增加抑制作用越明显;随着增殖受抑制,肺腺癌A549细胞上清外泌体中GPC1蛋白表达减少。

关键词：辐射肺腺癌细胞外泌体磷脂酰肌醇蛋白聚糖-1 细胞增殖

维普期刊数据库

Sesquiterpenoids,isolated from Commiphora opobalsamum,induce cell cycle arrest and inhibit androgen receptor transactivity in prostate cancer cells

在线全文

学校读者我要写书评

暂无评论

Sesquiterpenoids,isolated from Commiphora opobalsamum,induce...