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}
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.
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.