Evidence map›Paper›PMID 42019494›Full record

ArticleCell chemical biology2026

NEK7 Cys298 is important for NLRP3 inflammasome and targetable by dimethyl fumarate.

Yandong Zhang, Helena Lindner, Brian So, Zirong Chen, Haoyang Li, Jiashu Xu, Jiahe Wang, Jie Xu, Alexandru M Petre, Mark D Distefano and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

12 authors.

Yandong ZhangDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA; Department of Medicine and Department of Chemistry, University of Chicago, Chicago, IL, USA.
Helena LindnerDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Brian SoDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Zirong ChenDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA.
Haoyang LiDepartment of Medicine and Department of Chemistry, University of Chicago, Chicago, IL, USA.
Jiashu XuDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA; Department of Medicine and Department of Chemistry, University of Chicago, Chicago, IL, USA.
Jiahe WangDepartment of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA; Department of Medicine and Department of Chemistry, University of Chicago, Chicago, IL, USA.
Jie XuDepartment of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
Alexandru M PetreDepartment of Chemistry, University of Minnesota, Minneapolis, MN, USA.
Mark D DistefanoDepartment of Chemistry, University of Minnesota, Minneapolis, MN, USA.
Gabriel NúñezDepartment of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA; Center for Infectious Disease Education and Research (CIDER), Osaka University, Suita, Japan.
Hening LinHoward Hughes Medical Institute, Department of Chemistry and Chemical Biology, Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Howard Hughes Medical Institute, Department of Medicine and Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA. Electronic address: linh1@uchicago.edu.

Funding

Design and development of HDAC11-specific chemical inhibitors for disease treatmentsR01AI153110 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI LIN, HENING, MILLER, ROBERT H. · 2021 to 2025
$3.5M
Cryopyrin Signaling in Inflammation and Innate ImmunityR01AI063331 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NUNEZ, GABRIEL · 2005 to 2015
$3.3M
Chemical Approaches for Exploring Protein Prenylation in Living CellsR35GM141853 · NIGMS · UNIVERSITY OF MINNESOTA · PI MARK D DISTEFANO · 2021 to 2026
$2.4M
NIAID NIH HHS R01 AI063331NIAID NIH HHS R01 AI153110NIGMS NIH HHS R35 GM141853
6 · The paper itself

Abstract

Dimethyl fumarate (DMF), a cysteine targeting agent, is clinically used to treat multiple sclerosis and psoriasis. However, its precise molecular mechanism remains incompletely understood. Here, we investigated the effects of DMF on NLRP3 inflammasome activation. DMF suppresses NLRP3 inflammasome activity at both the priming and activation steps. Using chemoproteomics, we identified DMF targets in macrophages, including IRAK3/4 and RELA/B involved in the NLRP3 priming step, NEK7 involved in NLRP3 early activation, and GSDMD involved in NLRP3 late activation. To understand how DMF inhibits NLRP3 early activation, we showed that DMF modifies NEK7 Cys298 to disrupt NLRP3-NEK7 interaction and inflammasome activation. Interestingly, NEK7 Cys298 is critical for NLRP3 inflammasome activation. This study provides mechanistic insights into DMF's immunomodulatory effects and suggests that targeting NEK7 Cys298 can be a novel strategy for inflammatory diseases. Our work highlights the utility of DMF to identify functionally important cysteine residues in immune signaling pathways.

Indexed as

CysteineDimethyl FumarateInflammasomesNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 ProteinAnimalsHumansMacrophagesMiceCysteineDimethyl FumarateInflammasomesNEK7 protein, humanNek7 protein, mouseNIMA-Related KinasesNLR Family, Pyrin Domain-Containing 3 Proteindimethyl fumarateinflammasomeinnate immunityNEK7NLRP3

Identifiers

PMID42019494
PMCPMC13108522

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Registered trials

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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.