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PXD030989

PXD030989 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAlpha-1-antitrypsin binds to the glucocorticoid receptor with anti-inflammatory and anti-mycobacterial significance in macrophages
DescriptionAlpha-1-antitrypsin (AAT), a serine protease inhibitor produced mainly by the liver, is the third most abundant protein in plasma. Individuals who possess homozygous Z-AAT genotype have severe AAT deficiency and are at risk for early-onset emphysema, bronchiectasis, cirrhosis, panniculitis, and vasculitis. While a canonical receptor for AAT has not been identified, AAT can be internalized into the cytoplasm and is known to affect gene regulation. Since AAT has significant anti-inflammatory properties affecting many cell types including macrophages, we examined whether AAT binds the cytoplasmic glucocorticoid receptor (GR) in macrophages. We report the novel finding that AAT binds to GR in macrophages using several approaches, including co-immunoprecipitation, mass spectrometry, microscale thermophoresis, and in silico molecular modeling. We further demonstrate that AAT induction of angiopoietin-like 4 protein and AAT inhibition of lipopolysaccharide-induced nuclear factor-kappa B activation and interleukin-8 production are mediated, in part, through AAT–GR interaction. Furthermore, this interaction contributes to a host-protective role against Mycobacterium tuberculosis in macrophages. The interaction of AAT and GR described in this study identifies a mechanism for the anti-inflammatory and host-protective properties of AAT.
HostingRepositoryPRIDE
AnnounceDate2022-08-24
AnnouncementXMLSubmission_2022-08-24_15:49:47.547.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD030989
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMonika Dzieciatkowska
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-01-16 09:23:25ID requested
12022-08-24 15:49:47announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: glucocorticoids, corticosteroids, transcriptional activator, tuberculosis, alpha-1-antitrypsin
Contact List
Edward D. Chan1
contact affiliationNational Jewish Health
contact emailchane@njhealth.org
lab head
Monika Dzieciatkowska
contact affiliationUC Denver
contact emailmonika.dzieciatkowska@ucdenver.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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