Evidence map›Paper›PMID 27625306›Full record

ArticleScience signaling2016

Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells.

Megan M Blewett, Jiji Xie, Balyn W Zaro, Keriann M Backus, Amnon Altman, John R Teijaro, Benjamin F Cravatt

Open access · greenAbstract read
In one paragraph

Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
9.9field-weighted citation impact, top 1% 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

99 citing papers in PubMed, 186 citations in OpenAlex.

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  11. Profiling the landscape of cysteine posttranslational modifications in brain aging and neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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39 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

7 authors at 2 institutions in 1 country.

Megan M BlewettDepartment of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Jiji XieDivision of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
Balyn W ZaroDepartment of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Keriann M BackusDepartment of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Amnon AltmanDivision of Cell Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
John R TeijaroDepartment of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. teijaro@scripps.edu cravatt@scripps.edu.
Benjamin F CravattDepartment of Chemical Physiology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. teijaro@scripps.edu cravatt@scripps.edu.
La Jolla Institute for Immunology · USScripps Research Institute · US

Funding

Chemical Approaches for Activity-Based ProteomicsR37CA087660 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F · 2009 to 2018
$3.1M
CHEMICAL APPROACHES FOR ACTIVITY BASED PROTEOMICSR01CA087660 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI CRAVATT, BENJAMIN F · 2000 to 2008
$2.8M
Fragment-Based Ligand Discovery in ProteomesF32GM108208 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI BACKUS, KERIANN MARIE · 2013 to 2014
$102k
NCI NIH HHS R01 CA087660NCI NIH HHS R37 CA087660NIGMS NIH HHS F32 GM108208
6 · The paper itself

Abstract

Dimethyl fumarate (DMF) is an electrophilic drug that is used to treat autoimmune conditions, including multiple sclerosis and psoriasis. The mechanism of action of DMF is unclear but may involve the covalent modification of proteins or DMF serving as a prodrug that is converted to monomethyl fumarate (MMF). We found that DMF, but not MMF, blocked the activation of primary human and mouse T cells. Using a quantitative, site-specific chemical proteomic platform, we determined the DMF sensitivity of >2400 cysteine residues in human T cells. Cysteines sensitive to DMF, but not MMF, were identified in several proteins with established biochemical or genetic links to T cell function, including protein kinase Cθ (PKCθ). DMF blocked the association of PKCθ with the costimulatory receptor CD28 by perturbing a CXXC motif in the C2 domain of this kinase. Mutation of these DMF-sensitive cysteines also impaired PKCθ-CD28 interactions and T cell activation, designating the C2 domain of PKCθ as a key functional, electrophile-sensing module important for T cell biology.

Indexed as

ProteomicsAnimalsCD28 AntigensCysteineDimethyl FumarateHumansLymphocyte ActivationMiceMice, KnockoutProtein Kinase CProteomeT-LymphocytesCD28 AntigensCysteineDimethyl FumarateProtein Kinase Cprotein kinase C etaProteome

Identifiers

PMID27625306
PMCPMC5068918
OpenAlexW2519889757

What OpenQuestion holds

Textmetadata
LicenceTDM
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.