PXD052433-1

PXD052433 is an original dataset announced via ProteomeXchange.

Title	LPS-induced TIR domain complex acetylation activated TLR4/MAL/MyD88 signal pathway in sepsis
Description	Among the diseases caused by Toll-like receptor 4 (TLR4) abnormal activation by bacterial endotoxin, sepsis is the most dangerous one. The reprogramming of macrophages plays a crucial role in orchestrating the pathogenesis of sepsis. However, the precise mechanism underlying TLR4 activation in macrophages remained incompletely understood. Our studies revealed that upon lipopolysaccharide (LPS) stimulation, CREB-binding protein (CBP) was recruited to the TLR4 signalosome complex and resulted in pronounced acetylation in the TIR domains of TLR4, Myeloid differentiation factor 88 (MyD88) and MyD88 adapter-like (MAL), which significantly enhanced the activation of the NF-κB signaling pathway and polarization of M1 macrophages. In sepsis patients, significantly elevated TLR4-TIR acetylation was detected in CD16+ monocytes combined with elevated expression of M1 macrophage markers and production of pro-inflammatory cytokines. In contrast, histone deacetylase 1 (HDAC1) served as a key deacetylase in the deacetylation of the TIR domain complex. The inhibition of HDAC1 accelerated sepsis-associated syndromes, while the inhibition of CBP alleviated this process. Overall, our findings highlighted the crucial role of TIR domain complex acetylation in the regulation of inflammatory immune response and suggested that the reversible acetylation of the complex emerged as a promising therapeutic target for M1 macrophages during the progression of sepsis.
HostingRepository	PRIDE
AnnounceDate	2024-08-01
AnnouncementXML	Submission_2024-08-01_05:18:01.267.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xingxing Wu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-21 02:09:37	ID requested
⏵ 1	2024-08-01 05:18:01	announced

Dataset with its publication pending

submitter keyword: TLR4,Myd88,sepsis

Clinical Medicine
contact affiliation	Zhejiang Provincial People’s Hospital
contact email	18504292075@163.com
lab head
Xingxing Wu
contact affiliation	15869047982
contact email	2950889085@qq.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/2024/08/PXD052433

PRIDE project URI

• PRIDE
  1. PXD052433
     1. Label: PRIDE project
     2. Name: LPS-induced TIR domain complex acetylation activated TLR4/MAL/MyD88 signal pathway in sepsis