Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation
2018-04-24
Source PublicationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN0027-8424
Volume115Issue:17Pages:E4051-E4060
Status已发表
DOI10.1073/pnas.1801340115
Abstract

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.

Keywordgenome-wide CRISPR screen TCR signaling FAM49B Rac1 actin cytoskeleton
Indexed BySCI ; SCIE
Funding ProjectNIH[R37AI114575]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000430697500025
PublisherNATL ACAD SCIENCES
WOS KeywordRECEPTOR ; COMPLEX ; TCR ; CYTOSKELETON ; PROTEIN ; EXPRESSION ; ADAPTER ; RAC1 ; REORGANIZATION ; TRANSLOCATION
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/20844
Collection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
Co-First AuthorJiang, Yong
Corresponding AuthorWei, Lai; Weiss, Arthur; Wang, Haopeng
Affiliation
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
First Author AffilicationSchool of Life Science and Technology
Corresponding Author AffilicationSchool of Life Science and Technology
First Signature AffilicationSchool of Life Science and Technology
Recommended Citation
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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