PXD020964 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | IL6-regulated CDk8-mediated phosphoproteome of human primary Th1 cells |
Description | Cytokines are highly pleiotropic ligands that critically contribute to a balanced immune response. We have an incomplete understanding of how cytokines elicit their functional pleiotropy, which has limited their therapeutic efficacy. Here, using Interleukin-6 (IL-6) as a model system, we have performed detailed phosphoproteomic and transcriptomic studies in human CD4 + T helper (Th)-1 cells to address the molecular bases defining cytokine functional pleiotropy. We have identified cyclin dependent kinase (CDK)8 as a new negative regulator of transcriptional activities of signal transducer and activator of transcription (STAT)3. We found that CDK8 is a major regulator of the IL-6 phosphoproteome and interacts with STAT3 in the nucleus upon IL-6 stimulation. Inhibition of CDK8 activity, using specific small molecules inhibitors, reduced the IL-6-induced phosphoproteome by 23% in Th-1 cells, including STAT3 S727 phosphorylation. STAT3 binding to target DNA sites in the genome was increased upon CDK8 inhibition, which resulted in a concomitant increase in STAT3 mediated transcriptional activity. Importantly, inhibition of CDK8 activity under Th-17 polarizing conditions resulted in an enhancement of Th-17 differentiation. Our results support a model where CDK8 regulates STAT3 transcriptional processivity via modulation of its gene loci resident time, critically contributing to diversification of IL-6 responses. |
HostingRepository | PRIDE |
AnnounceDate | 2020-12-23 |
AnnouncementXML | Submission_2020-12-23_11:13:25.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jonathan Martinez Fabregas |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-08-17 22:30:10 | ID requested | |
⏵ 1 | 2020-12-23 11:13:25 | announced | |
2 | 2021-04-06 23:43:02 | announced | 2021-04-07: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: IL6, human Th1 cells, CDK8 inhibitor, MSC2530818 |
Contact List
Ignacio Moraga Gonzalez |
contact affiliation | Cell Signaling and Immunology School of Life Sciences University of Dundee |
contact email | i.moragagonzalez@dundee.ac.uk |
lab head | |
Jonathan Martinez Fabregas |
contact affiliation | Cell Signaling and Immunology |
contact email | jmartinezfabregas@dundee.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020964
- Label: PRIDE project
- Name: IL6-regulated CDk8-mediated phosphoproteome of human primary Th1 cells