PXD039815

PXD039815 is an original dataset announced via ProteomeXchange.

Title	TDAG51 is a novel coactivator of FoxO1
Description	Tight regulation of Toll-like receptor (TLR)-mediated inflammatory responses is important in innate immunity. Here, we show that T cell death-associated gene 51 (TDAG51/PHLDA1) is a novel coactivator of the transcription factor FoxO1, regulating inflammatory mediator production in the lipopolysaccharide (LPS)-induced inflammatory response. TDAG51 induction by LPS stimulation was mediated by the TLR2/4 signaling pathway in bone marrow-derived macrophages (BMMs). LPS-induced inflammatory mediator production was significantly decreased in TDAG51-deficient BMMs. In TDAG51-deficient mice, LPS- or pathogenic Escherichia coli infection-induced lethal shock was reduced by decreasing serum proinflammatory cytokine levels. The recruitment of 14-3-3 to FoxO1 was competitively inhibited by the TDAG51-FoxO1 interaction, leading to blockade of FoxO1 cytoplasmic translocation and thereby strengthening FoxO1 nuclear accumulation. TDAG51/FoxO1 double-deficient BMMs showed significantly reduced inflammatory mediator production compared with TDAG51- or FoxO1-deficient BMMs. TDAG51/FoxO1 double deficiency protected mice against LPS- or pathogenic E. coli infection-induced lethal shock by weakening the systemic inflammatory response. Thus, these results indicate that TDAG51 acts as a coactivator of the transcription factor FoxO1, leading to strengthened FoxO1 activity in the LPS-induced inflammatory response.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_06:48:26.142.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hye-Won Park
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	2023-02-03 01:44:17	ID requested
1	2023-06-23 17:18:20	announced
⏵ 2	2023-11-14 06:48:26	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, LPS, PHLDA1, TLR, inflammatory response, FoxO1, TDAG51

Jaerang Rho
contact affiliation	Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Korea
contact email	jrrho@cnu.ac.kr
lab head
Hye-Won Park
contact affiliation	Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Korea
contact email	phw0422@naver.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/2023/06/PXD039815

PRIDE project URI

• PRIDE
  1. PXD039815
     1. Label: PRIDE project
     2. Name: TDAG51 is a novel coactivator of FoxO1