Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation
2018-04-24
发表期刊PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN0027-8424
卷号115期号:17页码:E4051-E4060
发表状态已发表
DOI10.1073/pnas.1801340115
摘要

Despite decades of research, mechanisms controlling T cell activation remain only partially understood, which hampers T cell-based immune cancer therapies. Here, we performed a genome-wide CRISPR screen to search for genes that regulate T cell activation. Our screen confirmed many of the known regulators in proximal T cell receptor signaling and, importantly, also uncovered a previously uncharacterized regulator, FAM49B (family with sequence similarity 49 member B). FAM49B deficiency led to hyperactivation of Jurkat T cells following T cell receptor stimulation, as indicated by enhancement of CD69 induction, PAK phosphorylation, and actin assembly. FAM49B directly interacted with the active form of the small GTPase Rac, and genetic disruption of the FAM49BRac interaction compromised FAM49B function. Thus, FAM49B inhibits T cell activation by repressing Rac activity and modulating cytoskeleton reorganization.

关键词genome-wide CRISPR screen TCR signaling FAM49B Rac1 actin cytoskeleton
收录类别SCI ; SCIE
资助项目NIH[R37AI114575]
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000430697500025
出版者NATL ACAD SCIENCES
WOS关键词RECEPTOR ; COMPLEX ; TCR ; CYTOSKELETON ; PROTEIN ; EXPRESSION ; ADAPTER ; RAC1 ; REORGANIZATION ; TRANSLOCATION
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/20844
专题生命科学与技术学院
生命科学与技术学院_PI研究组_王皞鹏组
iHuman研究所_特聘教授组_Andrej Sali组
生命科学与技术学院_公共科研平台_组学分析平台
iHuman研究所_PI研究组_赵素文组
生命科学与技术学院_硕士生
生命科学与技术学院_博士生
共同第一作者Jiang, Yong
通讯作者Wei, Lai; Weiss, Arthur; Wang, Haopeng
作者单位
1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Univ Calif San Francisco, Dept Microbiol & Immunol, WM Keck Ctr Noncoding RNAs, Ctr Diabet, San Francisco, CA 94143 USA
5.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
6.Univ Calif San Francisco, Dept Med, Rosalind Russell & Ephraim P Engleman Rheumatol R, Div Rheumatol, San Francisco, CA 94143 USA
7.Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
8.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China
第一作者单位生命科学与技术学院
通讯作者单位生命科学与技术学院
第一作者的第一单位生命科学与技术学院
推荐引用方式
GB/T 7714
Shang, Wanjing,Jiang, Yong,Boettcher, Michael,et al. Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2018,115(17):E4051-E4060.
APA Shang, Wanjing.,Jiang, Yong.,Boettcher, Michael.,Ding, Kang.,Mollenauer, Marianne.,...&Wang, Haopeng.(2018).Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,115(17),E4051-E4060.
MLA Shang, Wanjing,et al."Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 115.17(2018):E4051-E4060.
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