Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processing
Increasing evidence indicates that caspase recruitment domain (CARD)‐mediated caspase‐1 (CASP1) assembly is an essential process for its activation and subsequent interleukin (IL)‐1β release, leading to the initiation of inflammation. Both CARD16 and CARD17 were previously reported as inhibitory hom...
Main Authors: | , , , , , , , , , , |
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Wiley
2015-01-01
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Series: | FEBS Open Bio |
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Online Access: | https://doi.org/10.1016/j.fob.2015.04.011 |
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author | Tadayoshi Karasawa Akira Kawashima Fumitake Usui Hiroaki Kimura Koumei Shirasuna Yoshiyuki Inoue Takanori Komada Motoi Kobayashi Yoshiko Mizushina Junji Sagara Masafumi Takahashi |
author_facet | Tadayoshi Karasawa Akira Kawashima Fumitake Usui Hiroaki Kimura Koumei Shirasuna Yoshiyuki Inoue Takanori Komada Motoi Kobayashi Yoshiko Mizushina Junji Sagara Masafumi Takahashi |
author_sort | Tadayoshi Karasawa |
collection | DOAJ |
description | Increasing evidence indicates that caspase recruitment domain (CARD)‐mediated caspase‐1 (CASP1) assembly is an essential process for its activation and subsequent interleukin (IL)‐1β release, leading to the initiation of inflammation. Both CARD16 and CARD17 were previously reported as inhibitory homologs of CASP1; however, their molecular function remains unclear. Here, we identified that oligomerization activity allows CARD16 to function as a CASP1 activator. We investigated the molecular characteristics of CARD16 and CARD17 in transiently transfected HeLa cells. Although both CARD16 and CARD17 interacted with CASP1CARD, only CARD16 formed a homo‐oligomer. Oligomerized CARD16 formed a filament‐like structure with CASP1CARD and a speck with apoptosis‐associated speck‐like protein containing a CARD. A filament‐like structure formed by CARD16 promoted CASP1 filament assembly and IL‐1β release. In contrast, CARD17 did not form a homo‐oligomer or filaments and inhibited CASP1‐dependent IL‐1β release. Mutated CARD16D27G, mimicking the CARD17 amino acid sequence, formed a homo‐oligomer but failed to form a filament‐like structure. Consequently, CARD16D27G weakly promoted CASP1 filament assembly and subsequent IL‐1β release. These results suggest that oligomerized CARD16 promotes CARD‐mediated molecular assembly and CASP1 activation. |
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issn | 2211-5463 |
language | English |
last_indexed | 2024-04-13T06:37:39Z |
publishDate | 2015-01-01 |
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series | FEBS Open Bio |
spelling | doaj.art-95e95b4fde7c4e91830b0160ad8847022022-12-22T02:57:50ZengWileyFEBS Open Bio2211-54632015-01-015134835610.1016/j.fob.2015.04.011Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processingTadayoshi Karasawa0Akira Kawashima1Fumitake Usui2Hiroaki Kimura3Koumei Shirasuna4Yoshiyuki Inoue5Takanori Komada6Motoi Kobayashi7Yoshiko Mizushina8Junji Sagara9Masafumi Takahashi10Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanDepartment of Molecular Oncology, Shinshu University Graduate School of Medicine, Nagano, JapanDivision of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, JapanIncreasing evidence indicates that caspase recruitment domain (CARD)‐mediated caspase‐1 (CASP1) assembly is an essential process for its activation and subsequent interleukin (IL)‐1β release, leading to the initiation of inflammation. Both CARD16 and CARD17 were previously reported as inhibitory homologs of CASP1; however, their molecular function remains unclear. Here, we identified that oligomerization activity allows CARD16 to function as a CASP1 activator. We investigated the molecular characteristics of CARD16 and CARD17 in transiently transfected HeLa cells. Although both CARD16 and CARD17 interacted with CASP1CARD, only CARD16 formed a homo‐oligomer. Oligomerized CARD16 formed a filament‐like structure with CASP1CARD and a speck with apoptosis‐associated speck‐like protein containing a CARD. A filament‐like structure formed by CARD16 promoted CASP1 filament assembly and IL‐1β release. In contrast, CARD17 did not form a homo‐oligomer or filaments and inhibited CASP1‐dependent IL‐1β release. Mutated CARD16D27G, mimicking the CARD17 amino acid sequence, formed a homo‐oligomer but failed to form a filament‐like structure. Consequently, CARD16D27G weakly promoted CASP1 filament assembly and subsequent IL‐1β release. These results suggest that oligomerized CARD16 promotes CARD‐mediated molecular assembly and CASP1 activation.https://doi.org/10.1016/j.fob.2015.04.011CaspaseCytokineInflammationInterleukin |
spellingShingle | Tadayoshi Karasawa Akira Kawashima Fumitake Usui Hiroaki Kimura Koumei Shirasuna Yoshiyuki Inoue Takanori Komada Motoi Kobayashi Yoshiko Mizushina Junji Sagara Masafumi Takahashi Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processing FEBS Open Bio Caspase Cytokine Inflammation Interleukin |
title | Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processing |
title_full | Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processing |
title_fullStr | Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processing |
title_full_unstemmed | Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processing |
title_short | Oligomerized CARD16 promotes caspase‐1 assembly and IL‐1β processing |
title_sort | oligomerized card16 promotes caspase 1 assembly and il 1β processing |
topic | Caspase Cytokine Inflammation Interleukin |
url | https://doi.org/10.1016/j.fob.2015.04.011 |
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