Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation
Nuclear factor κB (NF-κB) subunits comprise a family of eukaryotic transcription factors that are critically involved in cell proliferation, inflammation, and apoptosis. Under basal conditions, NF-κB subunits are kept under inhibitory regulation by physical interaction with NF-κB inhibitors (IκB sub...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , |
| التنسيق: | article |
| منشور في: |
2007
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| الوصول للمادة أونلاين: | http://hdl.handle.net/11073/25064 |
| الوسوم: |
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| _version_ | 1864513441674297344 |
|---|---|
| author | Majdalawieh, Amin |
| author2 | Zhang, Lei Ro, Hyo-Sung |
| author2_role | author author |
| author_facet | Majdalawieh, Amin Zhang, Lei Ro, Hyo-Sung |
| author_role | author |
| dc.creator.none.fl_str_mv | Majdalawieh, Amin Zhang, Lei Ro, Hyo-Sung |
| dc.date.none.fl_str_mv | 2007 2022-11-28T09:52:06Z 2022-11-28T09:52:06Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | Majdalawieh A, Zhang L, Ro HS. (2007) Adipocyte enhancer-binding protein-1 promotes macrophage inflammatory responsiveness by up-regulating NF-κB via IκBα negative regulation. Molecular Biology of the Cell 18(3):930-942. https://doi.org/10.1091/mbc.e06-03-0217. 1939-4586 http://hdl.handle.net/11073/25064 10.1091/mbc.e06-03-0217 |
| dc.language.none.fl_str_mv | en_US |
| dc.publisher.none.fl_str_mv | The American Society for Cell Biology |
| dc.relation.none.fl_str_mv | https://doi.org/10.1091/mbc.e06-03-0217 |
| dc.title.none.fl_str_mv | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation |
| dc.type.none.fl_str_mv | Peer-Reviewed Published version info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Nuclear factor κB (NF-κB) subunits comprise a family of eukaryotic transcription factors that are critically involved in cell proliferation, inflammation, and apoptosis. Under basal conditions, NF-κB subunits are kept under inhibitory regulation by physical interaction with NF-κB inhibitors (IκB subunits) in the cytosol. Upon stimulation, IκB subunits become phosphorylated, ubiquitinated, and subsequently degraded, allowing NF-κB subunits to translocate to the nucleus and bind as dimers to κB responsive elements of target genes. Previously, we have shown that AEBP1 enhances macrophage inflammatory responsiveness by inducing the expression of various proinflammatory mediators. Herein, we provide evidence suggesting that AEBP1 manifests its proinflammatory function by up-regulating NF-κB activity via hampering IκBα, but not IκBβ, inhibitory function through protein–protein interaction mediated by the discoidin-like domain (DLD) of AEBP1. Such interaction renders IκBα susceptible to enhanced phosphorylation and degradation, subsequently leading to augmented NF-κB activity. Collectively, we propose a novel molecular mechanism whereby NF-κB activity is modulated by means of protein–protein interaction involving AEBP1 and IκBα. Moreover, our study provides a plausible mechanism explaining the differential regulatory functions exhibited by IκBα and IκBβ in various cell types. We speculate that AEBP1 may serve as a potential therapeutic target for the treatment of various chronic inflammatory diseases and cancer. |
| format | article |
| id | aus_a8ed065d13f9dea7782a97bad43f1954 |
| identifier_str_mv | Majdalawieh A, Zhang L, Ro HS. (2007) Adipocyte enhancer-binding protein-1 promotes macrophage inflammatory responsiveness by up-regulating NF-κB via IκBα negative regulation. Molecular Biology of the Cell 18(3):930-942. https://doi.org/10.1091/mbc.e06-03-0217. 1939-4586 10.1091/mbc.e06-03-0217 |
| language_invalid_str_mv | en_US |
| network_acronym_str | aus |
| network_name_str | aus |
| oai_identifier_str | oai:repository.aus.edu:11073/25064 |
| publishDate | 2007 |
| publisher.none.fl_str_mv | The American Society for Cell Biology |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative RegulationMajdalawieh, AminZhang, LeiRo, Hyo-SungNuclear factor κB (NF-κB) subunits comprise a family of eukaryotic transcription factors that are critically involved in cell proliferation, inflammation, and apoptosis. Under basal conditions, NF-κB subunits are kept under inhibitory regulation by physical interaction with NF-κB inhibitors (IκB subunits) in the cytosol. Upon stimulation, IκB subunits become phosphorylated, ubiquitinated, and subsequently degraded, allowing NF-κB subunits to translocate to the nucleus and bind as dimers to κB responsive elements of target genes. Previously, we have shown that AEBP1 enhances macrophage inflammatory responsiveness by inducing the expression of various proinflammatory mediators. Herein, we provide evidence suggesting that AEBP1 manifests its proinflammatory function by up-regulating NF-κB activity via hampering IκBα, but not IκBβ, inhibitory function through protein–protein interaction mediated by the discoidin-like domain (DLD) of AEBP1. Such interaction renders IκBα susceptible to enhanced phosphorylation and degradation, subsequently leading to augmented NF-κB activity. Collectively, we propose a novel molecular mechanism whereby NF-κB activity is modulated by means of protein–protein interaction involving AEBP1 and IκBα. Moreover, our study provides a plausible mechanism explaining the differential regulatory functions exhibited by IκBα and IκBβ in various cell types. We speculate that AEBP1 may serve as a potential therapeutic target for the treatment of various chronic inflammatory diseases and cancer.Canadian Institute of Health Research (CIHR)Natural Science and Engineering Research Council (NSERC)The American Society for Cell Biology2022-11-28T09:52:06Z2022-11-28T09:52:06Z2007Peer-ReviewedPublished versioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfMajdalawieh A, Zhang L, Ro HS. (2007) Adipocyte enhancer-binding protein-1 promotes macrophage inflammatory responsiveness by up-regulating NF-κB via IκBα negative regulation. Molecular Biology of the Cell 18(3):930-942. https://doi.org/10.1091/mbc.e06-03-0217.1939-4586http://hdl.handle.net/11073/2506410.1091/mbc.e06-03-0217en_UShttps://doi.org/10.1091/mbc.e06-03-0217oai:repository.aus.edu:11073/250642024-08-22T11:59:48Z |
| spellingShingle | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation Majdalawieh, Amin |
| status_str | publishedVersion |
| title | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation |
| title_full | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation |
| title_fullStr | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation |
| title_full_unstemmed | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation |
| title_short | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation |
| title_sort | Adipocyte Enhancer-binding Protein-1 Promotes Macrophage Inflammatory Responsiveness by Up-Regulating NF-κB via IκBα Negative Regulation |
| url | http://hdl.handle.net/11073/25064 |