CDK8/19细胞周期蛋白依赖性激酶非依赖性作用机制的转基因小鼠研究

IF 0.2 Q4 MEDICINE, GENERAL & INTERNAL Bulletin of Russian State Medical University Pub Date : 2022-12-28 DOI:10.24075/brsmu.2022.066
Nina I Stavskaya, L. Ilchuk, YuD Okulova, MV Kubekina, EA Varlamova, YY Silaeva, A. Bruter
{"title":"CDK8/19细胞周期蛋白依赖性激酶非依赖性作用机制的转基因小鼠研究","authors":"Nina I Stavskaya, L. Ilchuk, YuD Okulova, MV Kubekina, EA Varlamova, YY Silaeva, A. Bruter","doi":"10.24075/brsmu.2022.066","DOIUrl":null,"url":null,"abstract":"The CDK8 cyclin-dependent transcription-associated kinase and its less studied paralog, CDK19, regulate the expression of the dependant genes via several mechanisms. CDK8/19 can directly phosphorylate some transcription factors (ICN, STAT1), but at the same time these kinases being a component of the mediator complex regulate transcrition via interaction with chromatin in the promoter and enhancer regions of appropriate genes. Recently the papers have appeared showing that CDK8/19 has kinase-independent mechanisms of action through comparison of the effects of the kinase activity genetic inactivation and chemical inhibition. The study was aimed to generate transgenic mice capable of the induced and tissue-specific expression of the kinase-negative (showing no phosphorylation activity) form of CDK8, CDK8 (D173A), which could be later used to study the CDK8 kinase-independent mechanisms of action in vivo. We obtained four F0 transgenic animals by microinjection of linear DNA into the pronucleus, two of these animals became the ancestors of two distinct lines. The copy number of the integrated construct was measured for all F0 and the lines generated. This model may be used to study the kinase-independent properties of the CDK8/19 proteins.","PeriodicalId":9344,"journal":{"name":"Bulletin of Russian State Medical University","volume":"1 1","pages":""},"PeriodicalIF":0.2000,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Transgenic mice for study of the CDK8/19 cyclin-dependent kinase kinase-independent mechanisms of action\",\"authors\":\"Nina I Stavskaya, L. Ilchuk, YuD Okulova, MV Kubekina, EA Varlamova, YY Silaeva, A. Bruter\",\"doi\":\"10.24075/brsmu.2022.066\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The CDK8 cyclin-dependent transcription-associated kinase and its less studied paralog, CDK19, regulate the expression of the dependant genes via several mechanisms. CDK8/19 can directly phosphorylate some transcription factors (ICN, STAT1), but at the same time these kinases being a component of the mediator complex regulate transcrition via interaction with chromatin in the promoter and enhancer regions of appropriate genes. Recently the papers have appeared showing that CDK8/19 has kinase-independent mechanisms of action through comparison of the effects of the kinase activity genetic inactivation and chemical inhibition. The study was aimed to generate transgenic mice capable of the induced and tissue-specific expression of the kinase-negative (showing no phosphorylation activity) form of CDK8, CDK8 (D173A), which could be later used to study the CDK8 kinase-independent mechanisms of action in vivo. We obtained four F0 transgenic animals by microinjection of linear DNA into the pronucleus, two of these animals became the ancestors of two distinct lines. The copy number of the integrated construct was measured for all F0 and the lines generated. This model may be used to study the kinase-independent properties of the CDK8/19 proteins.\",\"PeriodicalId\":9344,\"journal\":{\"name\":\"Bulletin of Russian State Medical University\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":0.2000,\"publicationDate\":\"2022-12-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bulletin of Russian State Medical University\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.24075/brsmu.2022.066\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bulletin of Russian State Medical University","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.24075/brsmu.2022.066","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

摘要

CDK8细胞周期蛋白依赖性转录相关激酶及其研究较少的同源物CDK19通过几种机制调节依赖性基因的表达。CDK8/19可以直接磷酸化一些转录因子(ICN,STAT1),但同时这些激酶作为介体复合物的组成部分,通过与适当基因的启动子和增强子区的染色质相互作用来调节转录。最近发表的论文表明,通过比较激酶活性的遗传失活和化学抑制的效果,CDK8/19具有激酶非依赖性的作用机制。该研究旨在产生能够诱导和组织特异性表达激酶阴性(无磷酸化活性)形式的CDK8,CDK8(D173A)的转基因小鼠,该转基因小鼠随后可用于研究CDK8激酶非依赖性的体内作用机制。我们通过将线性DNA显微注射到原核中获得了四只F0转基因动物,其中两只动物成为了两个不同系的祖先。测量所有F0和生成的行的集成结构的拷贝数。该模型可用于研究CDK8/19蛋白的激酶非依赖性特性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Transgenic mice for study of the CDK8/19 cyclin-dependent kinase kinase-independent mechanisms of action
The CDK8 cyclin-dependent transcription-associated kinase and its less studied paralog, CDK19, regulate the expression of the dependant genes via several mechanisms. CDK8/19 can directly phosphorylate some transcription factors (ICN, STAT1), but at the same time these kinases being a component of the mediator complex regulate transcrition via interaction with chromatin in the promoter and enhancer regions of appropriate genes. Recently the papers have appeared showing that CDK8/19 has kinase-independent mechanisms of action through comparison of the effects of the kinase activity genetic inactivation and chemical inhibition. The study was aimed to generate transgenic mice capable of the induced and tissue-specific expression of the kinase-negative (showing no phosphorylation activity) form of CDK8, CDK8 (D173A), which could be later used to study the CDK8 kinase-independent mechanisms of action in vivo. We obtained four F0 transgenic animals by microinjection of linear DNA into the pronucleus, two of these animals became the ancestors of two distinct lines. The copy number of the integrated construct was measured for all F0 and the lines generated. This model may be used to study the kinase-independent properties of the CDK8/19 proteins.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Bulletin of Russian State Medical University
Bulletin of Russian State Medical University MEDICINE, GENERAL & INTERNAL-
CiteScore
0.80
自引率
0.00%
发文量
59
期刊介绍: Bulletin of Russian State Medical University (Bulletin of RSMU, ISSN Print 2500–1094, ISSN Online 2542–1204) is a peer-reviewed medical journal of Pirogov Russian National Research Medical University (Moscow, Russia). The original language of the journal is Russian (Vestnik Rossiyskogo Gosudarstvennogo Meditsinskogo Universiteta, Vestnik RGMU, ISSN Print 2070–7320, ISSN Online 2070–7339). Founded in 1994, it is issued once every two months publishing articles on clinical medicine and medical and biological sciences, first of all oncology, neurobiology, allergy and immunology, medical genetics, medical microbiology and infectious diseases. Every issue is thematic. Deadlines for manuscript submission are announced in advance. The number of publications on topics in spite of the issue topic is limited. The journal accepts only original articles submitted by their authors, including articles that present methods and techniques, clinical cases and opinions. Authors must guarantee that their work has not been previously published elsewhere in whole or in part and in other languages and is not under consideration by another scientific journal. The journal publishes only one review per issue; the review is ordered by the editors.
期刊最新文献
Genetically encoded light-inducible sensor for nucleolar visualization Prefrontal cortex transcranial theta-burst stimulation frequency-dependent effects on cognitive functions Comparative bioinformatics analysis of antimicrobial resistance gene pool in the genomes of representatives of genus Corynebacterium Efficacy of the jawbone defect elimination Ischemic stroke with and without brachiocephalic artery dissections: results of comprehensive examination of patients
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1