PXD030989 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Alpha-1-antitrypsin binds to the glucocorticoid receptor with anti-inflammatory and anti-mycobacterial significance in macrophages |
Description | Alpha-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. |
HostingRepository | PRIDE |
AnnounceDate | 2022-08-24 |
AnnouncementXML | Submission_2022-08-24_15:49:47.547.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD030989 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Monika Dzieciatkowska |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-01-16 09:23:25 | ID requested | |
⏵ 1 | 2022-08-24 15:49:47 | announced | |
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 affiliation | National Jewish Health |
contact email | chane@njhealth.org |
lab head | |
Monika Dzieciatkowska |
contact affiliation | UC Denver |
contact email | monika.dzieciatkowska@ucdenver.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD030989
- Label: PRIDE project
- Name: Alpha-1-antitrypsin binds to the glucocorticoid receptor with anti-inflammatory and anti-mycobacterial significance in macrophages