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Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1

Abstract:

The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood1,2,3. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 an...

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Publication status:
Published
Peer review status:
Peer reviewed
Version:
Accepted Manuscript

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Publisher copy:
10.1038/nature25986

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Funding agency for:
Fischer, R
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Funding agency for:
Kessler, BM
Publisher:
Springer Nature Publisher's website
Journal:
Nature Journal website
Volume:
556
Issue:
7699
Pages:
113-117
Publication date:
2018-03-28
Acceptance date:
2018-02-09
DOI:
EISSN:
1476-4687
ISSN:
0028-0836
Pubs id:
pubs:833972
URN:
uri:a328d53b-ce28-4ce4-aefb-839754ab5322
UUID:
uuid:a328d53b-ce28-4ce4-aefb-839754ab5322
Local pid:
pubs:833972
Language:
English

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