PXD039083 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses |
Description | Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis and human cancers. However, the role of DCLK1 in atherosclerosis remains undefined. In this study, we identified up-regulated DCLK1 in macrophages in atherosclerotic lesions of ApoE-/- mice fed an HFD and determined that macrophage-specific DCLK1 deletion attenuates atherosclerosis by reducing inflammation in mice. Mechanistically, RNA sequencing analysis indicated that DCLK1 mediates oxLDL-induced inflammation via NF-κB signaling pathway in primary macrophages. Co-immunoprecipitation followed by LC-MS/MS analysis identified IKKβ as a binding protein of DCLK1. We confirmed that DCLK1 directly interacts with IKKβ and phosphorylates IKKβ at S177/181, thereby facilitating subsequent NF-κB activation and inflammatory gene expression in macrophages. Finally, a pharmacological inhibitor of DCLK1 prevents atherosclerotic progression and inflammation both in vitro and in vivo. Our findings demonstrated that macrophage DCLK1 promotes inflammatory atherosclerosis by binding to IKKβ and activating IKKβ/NF-κB. This study reports DCLK1 as a new IKKβ regulator in inflammation and a potential therapeutic target for inflammatory atherosclerosis. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_09:00:07.412.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | zhuqi huang |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-12-22 04:26:02 | ID requested | |
1 | 2023-02-27 05:53:34 | announced | |
⏵ 2 | 2023-11-14 09:00:07 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: LC-MS/MS |
Contact List
Guang Liang |
contact affiliation | Wenzhou Medical University |
contact email | 13780193226@163.com |
lab head | |
zhuqi huang |
contact affiliation | Wenzhou Medical University |
contact email | 13780193226@163.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039083
- Label: PRIDE project
- Name: Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses