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Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation | |
2018-04-24 | |
Source Publication | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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ISSN | 0027-8424 |
Volume | 115Issue:17Pages:E4051-E4060 |
Status | 已发表 |
DOI | 10.1073/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. |
Keyword | genome-wide CRISPR screen TCR signaling FAM49B Rac1 actin cytoskeleton |
Indexed By | SCI ; SCIE |
Funding Project | NIH[R37AI114575] |
WOS Research Area | Science & Technology - Other Topics |
WOS Subject | Multidisciplinary Sciences |
WOS ID | WOS:000430697500025 |
Publisher | NATL ACAD SCIENCES |
WOS Keyword | RECEPTOR ; COMPLEX ; TCR ; CYTOSKELETON ; PROTEIN ; EXPRESSION ; ADAPTER ; RAC1 ; REORGANIZATION ; TRANSLOCATION |
Original Document Type | Article |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | https://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 Author | Jiang, Yong |
Corresponding Author | Wei, 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 Affilication | School of Life Science and Technology |
Corresponding Author Affilication | School of Life Science and Technology |
First Signature Affilication | School 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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