PXD047058

PXD047058 is an original dataset announced via ProteomeXchange.

Title	Interactome analysis of Adenylyl cyclase-associated protein 1
Description	The direct inflammatory action of proprotein convertase subtilisin/kexin type 9 (PCSK9) is examined in vitro in monocytes and endothelial cells, as well as via an in vivo atherosclerosis animal model. PCSK9 exacerbates atherosclerosis in low-density lipoprotein receptor (LDLR)-/- mice, indicating an inflammatory effect mediated independently of the LDLR pathway. Here we show that Adenylyl cyclase-associated protein 1 (CAP1) is the main binding partner of PCSK9, serving a crucial role in the pro-inflammatory cascade of PCSK9 by enabling the induction of cytokines, the activation of Toll-like receptor 4 (TLR4), and the upregulation of scavenger receptors. We also present spleen tyrosine kinase (Syk) and protein kinase C delta (PKCδ) as pivotal mediators in the inflammatory cascade subsequent to PCSK9-CAP1 binding. In human peripheral blood mononuclear cells (PBMCs), serum PCSK9 levels are positively correlated with Syk, PKCδ, and p65 phosphorylation. Notably, the CAP1-fragment crystallizable region (CAP1-Fc) shows superior efficacy in mitigating PCSK9-mediated inflammatory signal transduction when compared with the PCSK9 inhibitor, evolocumab.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:45:43.956.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dohyun Han
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-18 08:45:38	ID requested
1	2024-06-16 01:16:56	announced
⏵ 2	2024-10-22 06:45:46	announced	2024-10-22: Updated project metadata.

10.1038/s41467-024-46336-2;

Shin D, Kim S, Lee H, Lee HC, Lee J, Park HW, Fukai M, Choi E, Choi S, Koo BJ, Yu JH, No G, Cho S, Kim CW, Han D, Jang HD, Kim HS, B, leading to atherosclerosis progression independently of LDL receptor. Nat Commun, 15(1):2789(2024) [pubmed]

submitter keyword: CAP1, Human, Interactome, PCSK9

Dohyun Han
contact affiliation	Proteomics core facility, Biomedical Research Institute, Seoul National University Hospital
contact email	hdh03@snu.ac.kr
lab head
Dohyun Han
contact affiliation	Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital
contact email	hdh03@snu.ac.kr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/06/PXD047058

PRIDE project URI

• PRIDE
  1. PXD047058
     1. Label: PRIDE project
     2. Name: Interactome analysis of Adenylyl cyclase-associated protein 1