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PXD047058

PXD047058 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleInteractome analysis of Adenylyl cyclase-associated protein 1
DescriptionThe 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 (PKCĪ“) 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, PKCĪ“, 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:45:43.956.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDohyun Han
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-11-18 08:45:38ID requested
12024-06-16 01:16:56announced
22024-10-22 06:45:46announced2024-10-22: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: CAP1, Human, Interactome, PCSK9
Contact List
Dohyun Han
contact affiliationProteomics core facility, Biomedical Research Institute, Seoul National University Hospital
contact emailhdh03@snu.ac.kr
lab head
Dohyun Han
contact affiliationProteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital
contact emailhdh03@snu.ac.kr
dataset submitter
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Dataset FTP location
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