PXD011252
PXD011252 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | Comparison of denatured and non-denatured FIH interactomes |
Description | Hypoxia occurs when tissue or cellular oxygen demand exceeds its supply and is a frequent condition in health and disease. Metazoans have developed a regulatory system that allows them to sense changes in oxygen levels in their microenvironment and adapt to them. The asparagine hydroxylase factor inhibiting HIF (FIH) regulates the transcriptional activity of the hypoxia-inducible factor (HIF), the master regulator of the cellular adaptive response to hypoxia [1, 2]. We recently identified the deubiquitinating enzyme ovarian tumour domain containing, ubiquitin aldehyde binding protein 1 (OTUB1) as novel bona fide FIH target protein with the hydroxylation occurring at the asparagine residue N22 [3, 4]. Surprisingly, in a follow-up investigation we observed a SDS-PAGE resistant interaction between FIH and OTUB1, resulting in a FIH-OTUB1 heterodimer (HD). Further analysis of the FIH-OTUB1 HD demonstrated that it is not linked by a disulfide bond, oxyester or thioester but likely through an amide bond. Interestingly, mutation of the hydroxylation acceptor site N22 in OTUB1 and genetic and pharmacologic inhibition of FIH prevented the formation of the heterodimer, demonstrating that HD formation is a consequence of FIH activity. To investigate if FIH-dependent stable protein complex formation was exclusive for OTUB1, we carried out a mass spectrometry (MS)-based FIH interactome analyses with denatured and non-denatured cell lysates (with or without SDS treatment and boiling). The results indicate the existence of further novel denaturing condition resistant protein complexes. 1. Mahon, P.C., K. Hirota, and G.L. Semenza, FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes & development, 2001. 15(20): p. 2675-86. 2. Lando, D., et al., FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes & development, 2002. 16(12): p. 1466-71. 3. Scholz, C.C., et al., Regulation of IL-1beta-induced NF-kappaB by hydroxylases links key hypoxic and inflammatory signaling pathways. Proc Natl Acad Sci U S A, 2013. 110(46): p. 18490-5. 4. Scholz, C.C., et al., FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1. PLoS biology, 2016. 14(1): p. e1002347. |
HostingRepository | PRIDE |
AnnounceDate | 2019-07-09 |
AnnouncementXML | Submission_2019-07-15_00:40:01.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Christina Pickel |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2018-10-02 05:45:16 | ID requested | |
1 | 2019-07-09 00:03:42 | announced | |
⏵ 2 | 2019-07-15 00:40:02 | announced | Updated publication reference for PubMed record(s): 31299612. |
Publication List
Pickel C, G, ΓΌ, nter J, Ruiz-Serrano A, Spielmann P, Fabrizio JA, Wolski W, Peet DJ, Wenger RH, Scholz CC, Oxygen-dependent bond formation with FIH regulates the activity of the client protein OTUB1. Redox Biol, 26():101265(2019) [pubmed] |
Keyword List
curator keyword: Biological |
submitter keyword: asparagine hydroxylase, HIF, hypoxia, oxygen, covalent bond, amide bond |
Contact List
Carsten Scholz | |
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contact affiliation | Institute of Physiology, University of Zurich, Switzerland |
contact email | carsten.scholz@uzh.ch |
lab head | |
Christina Pickel | |
contact affiliation | University of Zurich |
contact email | christina.pickel@uzh.ch |
dataset submitter |
Full Dataset Link List
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PRIDE project URI |
Repository Record List
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