A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling

Abstract In the present study, a new type of Caspase-1 homolog is identified from Crassostrea gigas (defined as CgCas1-2D). It is composed of 2×DSRM-CASc domain and has closer evolutionary relationship with mammalian Caspase-1s. The mRNA expressions of CgCas1-2D increase significantly after Vibrio s...

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Main Authors: Renle Chang, Jiejie Sun, Jinyuan Leng, Zihan Wang, Shuyi Mu, Yinan Li, Jie Wang, Linsheng Song
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08290-7
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author Renle Chang
Jiejie Sun
Jinyuan Leng
Zihan Wang
Shuyi Mu
Yinan Li
Jie Wang
Linsheng Song
author_facet Renle Chang
Jiejie Sun
Jinyuan Leng
Zihan Wang
Shuyi Mu
Yinan Li
Jie Wang
Linsheng Song
author_sort Renle Chang
collection DOAJ
description Abstract In the present study, a new type of Caspase-1 homolog is identified from Crassostrea gigas (defined as CgCas1-2D). It is composed of 2×DSRM-CASc domain and has closer evolutionary relationship with mammalian Caspase-1s. The mRNA expressions of CgCas1-2D increase significantly after Vibrio splendidus or LPS stimulation. Recombinant CgCas1-2D and its 2×DSRM and CASc domains all bind various PAMPs and bacteria. rCgCas1-2D shows the highest binding activity to human Caspase-1 substrate. Upon recognizing bacteria, CgCas1-2D co-localizes and interacts with CgGSDME, while it has no cleavage activity to CgGSDME. CgCas1-2D inhibits the histone methylation and acetylation levels and CgNF-κB/Rel nuclear translocation mediated by CgGSDME. In addition, CgCas1-2D suppresses the mRNA expression levels of cytokines mediated by GSDME-NF-κB/Rel axis. The results demonstrate that a new type of anti-inflammatory Caspase-1 identified from oyster upon recognizing various bacteria interacts with GSDME to inhibit the histone modification and NF-κB signaling to suppress the inflammation.
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spelling doaj-art-8639db321a32420f98ff1872d14f4f942025-08-20T02:03:38ZengNature PortfolioCommunications Biology2399-36422025-05-018111710.1038/s42003-025-08290-7A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signalingRenle Chang0Jiejie Sun1Jinyuan Leng2Zihan Wang3Shuyi Mu4Yinan Li5Jie Wang6Linsheng Song7Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityLiaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityLiaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityLiaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityLiaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityLiaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityLiaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityLiaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean UniversityAbstract In the present study, a new type of Caspase-1 homolog is identified from Crassostrea gigas (defined as CgCas1-2D). It is composed of 2×DSRM-CASc domain and has closer evolutionary relationship with mammalian Caspase-1s. The mRNA expressions of CgCas1-2D increase significantly after Vibrio splendidus or LPS stimulation. Recombinant CgCas1-2D and its 2×DSRM and CASc domains all bind various PAMPs and bacteria. rCgCas1-2D shows the highest binding activity to human Caspase-1 substrate. Upon recognizing bacteria, CgCas1-2D co-localizes and interacts with CgGSDME, while it has no cleavage activity to CgGSDME. CgCas1-2D inhibits the histone methylation and acetylation levels and CgNF-κB/Rel nuclear translocation mediated by CgGSDME. In addition, CgCas1-2D suppresses the mRNA expression levels of cytokines mediated by GSDME-NF-κB/Rel axis. The results demonstrate that a new type of anti-inflammatory Caspase-1 identified from oyster upon recognizing various bacteria interacts with GSDME to inhibit the histone modification and NF-κB signaling to suppress the inflammation.https://doi.org/10.1038/s42003-025-08290-7
spellingShingle Renle Chang
Jiejie Sun
Jinyuan Leng
Zihan Wang
Shuyi Mu
Yinan Li
Jie Wang
Linsheng Song
A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling
Communications Biology
title A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling
title_full A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling
title_fullStr A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling
title_full_unstemmed A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling
title_short A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling
title_sort new type of caspase 1 upon recognizing bacteria inhibits gsdme dependent histone modification and nf κb signaling
url https://doi.org/10.1038/s42003-025-08290-7
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