PXD039083-1

PXD039083 is an original dataset announced via ProteomeXchange.

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	2023-02-27
AnnouncementXML	Submission_2023-02-27_05:53:34.229.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	zhuqihuang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

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.

submitter keyword: LC-MS/MS

GuangLiang
contact affiliation	Wenzhou Medical University
contact email	13780193226@163.com
lab head
zhuqihuang
contact affiliation	Wenzhou Medical University
contact email	13780193226@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039083
     1. Label: PRIDE project
     2. Name: Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses