检索结果-南通市图书馆

MYC promotes global transcription in part by controlling P-TEFb complex formation via DNA-binding independent inhibition of CDK9 SUMOylation

引用

Science China(Life Sciences) 2023年第9期66卷 2167-2184页

作者： Qingqing Guan Zhaosu Chen Fang Yu Lingling Liu Yuanyong Huang Gang Wei Cheng-Ming Chiang Jiemin Wong Jiwen Li Shanghai Key Laboratory of Regulatory Biology Fengxian District Central Hospital-ECNU Joint Center of Translational MedicineInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Medicine UF Health Cancer CenterUniversity of FloridaGainesvilleFL 32610USA CAS Key Laboratory of Computational Biology Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Simmons Comprehensive Cancer Center Department of Pharmacologyand Department of BiochemistryUniversity of Texas Southwestern Medical CenterDallas TX 75390USA

MYC is an oncogenic transcription factor with a novel role in enhancing global transcription when overexpressed. However, how MYC promotes global transcription remains controversial. Here, we used a series of MYC mutants to dissect the molecular basis for MYC-driven global transcription. We found that MYC mutants deficient in DNA binding or known transcriptional activation activities can still promote global transcription and enhance serine 2 phosphorylation(Ser2P) of the RNA polymerase(Pol) II Cterminal domain(CTD), a hallmark of active elongating RNA Pol II. Two distinct regions within MYC can promote global transcription and Ser2P of Pol II CTD. The ability of various MYC mutants to promote global transcription and Ser2P correlates with their ability to suppress CDK9 SUMOylation and enhance positive transcription elongation factor b(P-TEFb) complex formation. We showed that MYC suppresses CDK9 SUMOylation by inhibiting the interaction between CDK9 and SUMO enzymes including UBC9 and PIAS1. Furthermore, MYC's activity in enhancing global transcription positively contributes to its activity in promoting cell proliferation and transformation. Together, our study demonstrates that MYC promotes global transcription, at least in part, by promoting the formation of the active P-TEFb complex via a sequence-specific DNA-binding activity-independent manner.

关键词： MYC global transcription P-TEFb CDK9 SUMOylation cell transformation

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

Nucleolus localization of SpyCas9 affects its stability and interferes with host protein translation in mammalian cells

引用

Genes & Diseases 2022年第3期9卷 731-740页

作者： Renke Tan Wenhao Du Yiyang Liu Xiaoji Cong Meirong Bai Chenxiao Jiang Zengxia Li Minjia Tan Dengke K.Ma Qiang Huang Wei Jiang Yongjun Dang Key Laboratory of Metabolism and Molecular Medicine the Ministry of EducationDepartment of Biochemistry and Molecular BiologySchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghai 200032PR China State Key Laboratory of Genetic Engineering School of Life SciencesFudan UniversityShanghai 200043PR China Drug Discovery and Design Center State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203PR China Cardiovascular Research Institute University of CaliforniaSan FranciscoCA 94158USA

The CRISPR/Cas9 system,originally derived from the prokaryotic adaptive immune system,has been developed as efficient genome editing *** enables precise gene manipulation on chromosomal DNA through the specific binding of programmable sgRNA to target DNA,and the Cas9 protein,which has endonuclease activity,will cut a double strand break at specific ***,Cas9 is a foreign protein in mammalian cells,and the potential risks associated with its introduction into mammalian cells are not fully *** this study,we performed pull-down and mass spectrometry(MS)analysis of Streptococcus pyogenes Cas9(SpyCas9)interacting proteins in HEK293T cells and showed that the majority of Cas9-associated proteins identified by MS were localized in the ***,we further discovered that the Cas9 protein contains a sequence encoding a nucleolus detention signal(NoDS).Compared with wild-type(WT)Cas9,NoDS-mutated variants of Cas9(mCas9)are less stable,although their gene editing activity is minimally *** of WT Cas9,but not mCas9,causes general effects on transcription and protein translation in the host ***,identification of NoDS in Cas9 will improve the understanding of Cas9's biological function in vivo,and the removal of NoDS in Cas9 may enhance its safety for future clinical use.

关键词： CRISPR/Cas9 Gene editing global transcription Nucleolus detention signal Translation

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

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：