PXD053747 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TFAP2A supports HIF-1-dependent activation of hypoxia-inducible genes |
Description | Hypoxia can be established under pathological conditions, such as cancer, due to the imbalance between oxygen supply and consumption. Hypoxia Inducible Transcription Factor HIF-1 mediates the physiological response to hypoxia but also regulates multiple steps of carcinogenesis. Despite its well-defined oxygen-dependent activation, many aspects of HIF-1 transcriptional activity as well as interaction with chromatin remain elusive. We have recently shown that TFAP2A physically interacts with HIF-1 and hypoxia-dependent deSUMOylation of TFAP2A positively affects HIF-1 activity. We now present ChIP-seq analysis showing that TFAP2A resides together with HIF-1α on the promoters of a subset of hypoxia-regulated genes, the mRNA expression of which is downregulated by silencing of TFAP2A. Interestingly, CRISPR-mediated knockdown of TFAP2A expression under hypoxia decreased the occupancy of HIF-1α on these promoters and affected chromatin accessibility. Mechanistically, we reveal that the Ku70/Ku80 protein complex interacts with TFAP2A in a SUMO-dependent manner under hypoxia and participates in HIF-dependent gene expression. Moreover, using stable expression of TFAP2A forms that either lack or constitutively carry a SUMO modification, we could show that SUMOylation affects binding of TFAP2A to chromatin. Overall, our data suggest that TFAP2A is an important co-regulator of the HIF-1-dependent transcriptional response to hypoxia and SUMOylation fine-tunes this regulation. As both TFAP2A and HIF-1 play critical roles in cancer progression, a detailed characterization of their crosstalk could lead to novel therapeutic strategies for targeting and killing cancer cells in hypoxic tumors. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-23 |
AnnouncementXML | Submission_2025-05-23_06:55:11.474.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Martina Samiotaki |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive HF-X |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-07-08 03:10:45 | ID requested | |
⏵ 1 | 2025-05-23 06:55:11 | announced | |
Publication List
Keyword List
submitter keyword: SUMOylation, TFAP2A,HIF-1α, HIF, SUMO |
Contact List
Georgia Chachami |
contact affiliation | Laboratory of Biochemistry Dept of Medicine University of Thessaly Biopolis 41500, Larissa Greece |
contact email | ghah@med.uth.gr |
lab head | |
Martina Samiotaki |
contact affiliation | Protein Analysis Laboratory
B.S.R.C. "Alexander Fleming",
Alexander Fleming Street 34
16672, Vari,
Greece |
contact email | samiotaki@fleming.gr |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD053747
- Label: PRIDE project
- Name: TFAP2A supports HIF-1-dependent activation of hypoxia-inducible genes