PXD037926

PXD037926 is an original dataset announced via ProteomeXchange.

Title	Endothelial OTUD1 promotes Ang II-induced vascular remodeling by deubiquitinating SMAD3
Description	Understanding the molecular mechanisms of pathological vascular remodeling is important for treating cardiovascular diseases and complications. Recent studies have highlighted a role of deubiquitinases in vascular pathophysiology. In this study, we investigated the role of a deubiquitinase, OTUD1, in angiotensin II (Ang II)-induced vascular remodeling. We identified upregulated OTUD1 in the vascular endothelium of Ang II-challenged mice and showed OTUD1 deletion attenuated vascular remodeling, collagen deposition, and EndMT. Conversely, OTUD1 overexpression aggravated these pathological changes both in vivo and in vitro. Mechanistically, SMAD3 was identified as a substrate of OTUD1 using co-immunoprecipitation followed with LC-MS/MS. We found OTUD1 stabilizes SMAD3 and facilitates SMAD3/SMAD4 complex formation and subsequent nuclear translocation through both K48- and K63-linked deubiquitination. OTUD1-mediated SMAD3 activation regulate the transcription of genes involved in vascular EndMT and remodeling in HUVECs. Finally, SMAD3 inhibition reversed OTUD1-promoted vascular remodeling. Our findings demonstrate endothelial OTUD1 promoted Ang II-induced vascular remodeling by deubiquitinating SMAD3. This study identified SMAD3 as a target of OTUD1 and indicates OTUD1 as a potential therapeutic target for the diseases related to vascular remodeling.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:59:51.408.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

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-03 04:53:08	ID requested
1	2022-12-23 23:55:14	announced
⏵ 2	2023-11-14 08:59:51	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: HUVEC

LC-MS/MS

Zhuqi Huang
contact affiliation	Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
contact email	13780193226@163.com
lab head
zhuqi huang
contact affiliation	Wenzhou Medical University
contact email	13780193226@163.com
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/2022/12/PXD037926

PRIDE project URI

• PRIDE
  1. PXD037926
     1. Label: PRIDE project
     2. Name: Endothelial OTUD1 promotes Ang II-induced vascular remodeling by deubiquitinating SMAD3