Evidence map›Paper›PMID 29632189›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation.

Wanjing Shang, Yong Jiang, Michael Boettcher, Kang Ding, Marianne Mollenauer, Zhongyi Liu, Xiaofeng Wen, Chang Liu, Piliang Hao, Suwen Zhao and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

79 citing papers in PubMed, 117 citations in OpenAlex.

  1. SPRED2 Negatively Regulates CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Wanjing ShangSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
Yong JiangSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
Michael BoettcherW. M. Keck Center for Noncoding RNAs, Diabetes Center, Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.
Kang DingSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
Marianne MollenauerDivision of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA 94143.
Zhongyi LiuSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
Xiaofeng WenState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, China.
Chang LiuSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
Piliang HaoSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
Suwen ZhaoSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China.
Michael T McManusW. M. Keck Center for Noncoding RNAs, Diabetes Center, Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.
Lai WeiState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 510060 Guangzhou, China weil9@mail.sysu.edu.cn aweiss@medicine.ucsf.edu wanghp@shanghaitech.edu.cn.ORCID 0000-0002-3300-8506
Arthur WeissDivision of Rheumatology, Department of Medicine, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA 94143; weil9@mail.sysu.edu.cn aweiss@medicine.ucsf.edu wanghp@shanghaitech.edu.cn.
Haopeng WangSchool of Life Science and Technology, ShanghaiTech University, 201210 Shanghai, China; weil9@mail.sysu.edu.cn aweiss@medicine.ucsf.edu wanghp@shanghaitech.edu.cn.
ShanghaiTech University · CNChinese Academy of Sciences · CNHoward Hughes Medical Institute · USSun Yat-sen University · CNUniversity of California, San Francisco · US

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KRUMMEL, MATTHEW F · 2003 to 2019
$21.8M
The cell and molecular mechanisms underlying CD28 costimulationR37AI114575 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WEISS, ARTHUR · 2016 to 2023
$3.2M
Howard Hughes Medical InstituteNIAID NIH HHS R37 AI114575NIDDK NIH HHS P30 DK063720
6 · The paper itself

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 FAM49B-Rac interaction compromised FAM49B function. Thus, FAM49B inhibits T cell activation by repressing Rac activity and modulating cytoskeleton reorganization.

Indexed as

Lymphocyte ActivationActinsAntigens, CDAntigens, Differentiation, T-LymphocyteCD69 AntigensCRISPR-Cas SystemsCytoskeletonGenome-Wide Association StudyHumansJurkat CellsLectins, C-TypeNeoplasm ProteinsProto-Oncogene Proteins c-aktT-LymphocytesActinsAntigens, CDAntigens, Differentiation, T-LymphocyteCD69 AntigensLectins, C-TypeNeoplasm ProteinsProto-Oncogene Proteins c-aktactin cytoskeletonFAM49Bgenome-wide CRISPR screenRac1TCR signaling

Identifiers

PMID29632189
PMCPMC5924929
OpenAlexW2796942322

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.