ENKD1 modulates innate immune responses through enhanced geranylgeranyl pyrophosphate synthase activity

Inflammation is a crucial element of immune responses, with pivotal roles in host defenses against pathogens. Comprehensive understanding of the molecular mechanisms underlying inflammation is imperative for developing effective strategies to combat infectious diseases. Here, we conducted a screening analysis and identified enkurin domain-containing protein 1 (ENKD1) as a promising regulator of inflammation. We observed that ENKD1 expression was significantly reduced on activation of multiple Toll-like receptor (TLR) molecules. Deletion of ENKD1 resulted in enhanced innate immune system activation and exacerbation of septic inflammation. Mechanistically, ENKD1 interacted with geranylgeranyl diphosphate synthase 1 (GGPS1) and modulated its enzymatic activity, thereby influencing geranylgeranyl diphosphate production. This interaction ultimately led to Ras-related C3 botulinum toxin substrate 1 (RAC1) inactivation and suppression of pro-inflammatory signaling pathways. Our findings establish ENKD1 as a critical regulator of innate immune cell activation, underscoring its significant role in septic inflammation.

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Publication Details

Journal
Cell Reports
Published
2025-03-01
DOI
https://doi.org/10.1016/j.celrep.2025.115397
Citations
3
Primary Topic
ATP Synthase and ATPases Research
Type
article
Field-Weighted Citation Impact
2.42
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article

ENKD1 modulates innate immune responses through enhanced geranylgeranyl pyrophosphate synthase activity

Wei Xie, Yali Jin, Jun Zhou, Ruqian Yang et al.
3 citations
Cell Reports
ATP Synthase and ATPases Research
2.42
article

ENKD1 modulates innate immune responses through enhanced geranylgeranyl pyrophosphate synthase activity

Wei Xie, Yali Jin, Jun Zhou, Ruqian Yang, Sijin Wu, Wenqing Xu, Yan Li, Yixuan Wang, Tianyu Zhang, Jie Wang, Tianliang Li, Chaojun Li, Ting Song, Xiangfeng Chen, Xin Nie, Lulu Sun, Xiangrong Chen
article en
3 citations

Abstract

Inflammation is a crucial element of immune responses, with pivotal roles in host defenses against pathogens. Comprehensive understanding of the molecular mechanisms underlying inflammation is imperative for developing effective strategies to combat infectious diseases. Here, we conducted a screening analysis and identified enkurin domain-containing protein 1 (ENKD1) as a promising regulator of inflammation. We observed that ENKD1 expression was significantly reduced on activation of multiple Toll-like receptor (TLR) molecules. Deletion of ENKD1 resulted in enhanced innate immune system activation and exacerbation of septic inflammation. Mechanistically, ENKD1 interacted with geranylgeranyl diphosphate synthase 1 (GGPS1) and modulated its enzymatic activity, thereby influencing geranylgeranyl diphosphate production. This interaction ultimately led to Ras-related C3 botulinum toxin substrate 1 (RAC1) inactivation and suppression of pro-inflammatory signaling pathways. Our findings establish ENKD1 as a critical regulator of innate immune cell activation, underscoring its significant role in septic inflammation.

Cell ReportsVol. 44(3)
Qilu University of Technology (CN), Nankai University (CN), Shandong Normal University (CN), Shandong First Medical University (CN), State Key Laboratory of Medicinal Chemical Biology, State Key Laboratory of Pharmaceutical Biotechnology, Xi’an Jiaotong-Liverpool University (CN), Nanjing University (CN)
Openalex Percentile: Top 13%
ATP Synthase and ATPases Research
2.42
DOIOpen Access PDFOpenAlex
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