PXD007793

PXD007793 is an original dataset announced via ProteomeXchange.

Title	The autophagy receptor p62/SQSTM1 mediates anti-inflammatory actions of the selective glucocorticoid receptor modulator CpdA in macrophages
Description	Glucocorticoids are widely used to treat inflammatory disorders. Prolonged use results in side effects including osteoporosis, diabetes and obesity. The selective glucocorticoid receptor (GR) modulator Compound A (CpdA) exhibits an inflammation-suppressive effect, largely in absence of detrimental side effects. To understand the mechanistic differences between the classic glucocorticoid dexamethasone (DEX) and CpdA, we looked for proteins oppositely regulated using an unbiased proteomics approach. We found that the autophagy receptor p62 but not GR mediates the anti-inflammatory action of CpdA in macrophages. CpdA drives the upregulation of p62 by recruiting the NRF2 transcription factor to its promoter. Contrarily, the classic GR ligand dexamethasone recruits GR to p62 and other NRF2 controlled gene promoters, resulting in gene downregulation. Both DEX and CpdA are able to induce autophagy, albeit in a cell-type and time-dependent manner. Suppression of LPS-induced IL-6 and MCP1 genes in bone marrow-derived macrophages by CpdA is hampered upon p62 silencing, confirming that p62 is essential for the anti-inflammatory capacity of CpdA. Together, these results demonstrate how off-target mechanisms of selective GR ligands may establish a more efficient anti-inflammatory therapy
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:37:28.164.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Evy Timmerman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-19 05:13:15	ID requested
1	2022-06-03 00:46:08	announced
⏵ 2	2024-10-22 05:37:28	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: autophagy, p62/SQSTM1, inflammation, NRF2-signaling, CpdA,glucocorticoids, autophagy receptors, LC-MS/MS

Debosscher Karolien
contact affiliation	Prof. Dr. Karolien De Bosscher - Staff Scientist VIB-UGent Center for Medical Biotechnology Albert Baertsoenkaai 3 - 9000 Gent - Belgium
contact email	karolien.debosscher@vib-ugent.be
lab head
Evy Timmerman
contact affiliation	Ghent University - VIB
contact email	evy.timmerman@vib-ugent.be
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/2022/06/PXD007793

PRIDE project URI

• PRIDE
  1. PXD007793
     1. Label: PRIDE project
     2. Name: The autophagy receptor p62/SQSTM1 mediates anti-inflammatory actions of the selective glucocorticoid receptor modulator CpdA in macrophages