PXD027615

PXD027615 is an original dataset announced via ProteomeXchange.

Title	HUVEC 3xHA.FoxO3.A3.ER +4-OHT vs vector +4-OHT
Description	Forkhead Box O (FoxO) transcription factors are conserved proteins involved in the regulation of life span and age-related diseases, such as diabetes and cancer. Stress stimuli or growth factor deprivation promote nuclear localization and activation of FoxO proteins, which - depending on the cellular context - leads to cell cycle arrest or apoptosis. Moreover, FoxOs can control oxidative stress resistance and cell metabolism. In endothelial cells (ECs), they additionally regulate angiogenesis and may promote inflammation and vessel destabilization implicating a role of FoxOs in vascular diseases. In several cancers, FoxO transcription factors exert a tumor-suppressive function, due to their critical role in regulating proliferation and survival. Others and we have previously shown that FoxOs can regulate these processes via two different mechanisms: either by direct binding to FoxO-responsive elements (FRE) at the promoter of target genes or by a poorly understood alternative process that does not require direct DNA binding and regulates key targets in primary human ECs. Here we performed an interaction study in ECs to identify new nuclear FoxO3 interaction partners, which might contribute to FoxO-dependent gene regulation. Mass spectrometry analysis of FoxO3-interacting proteins revealed Transformation/Transcription Domain-Associated Protein (TRRAP), a member of multiple histone acetyltransferase (HAT) complexes, as novel binding partner of FoxO family proteins. TRRAP is required to support FoxO3 transactivation and FoxO3-dependent apoptosis in ECs via transcriptional activation of the proapoptotic Bcl-2 family member BIM. Moreover, FoxO-TRRAP interaction might explain FoxO-induced alternative gene regulation via TRRAP-dependent recruitment to target promoters lacking FRE sequences.
HostingRepository	PRIDE
AnnounceDate	2022-01-20
AnnouncementXML	Submission_2022-04-06_01:27:26.082.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marc Schmidt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-28 02:30:27	ID requested
1	2022-01-20 00:19:12	announced
⏵ 2	2022-04-06 01:27:26	announced	2022-04-06: Updated publication reference for PubMed record(s): 35151693.

Fusi L, Paudel R, Meder K, Schlosser A, Schrama D, Goebeler M, Schmidt M, Interaction of transcription factor FoxO3 with histone acetyltransferase complex subunit TRRAP modulates gene expression and apoptosis. J Biol Chem, 298(3):101714(2022) [pubmed]

submitter keyword: human, endothelium, HUVEC, FoxO3

Marc Schmidt
contact affiliation	University Hospital Wuerzburg, Department of Dermatology, Venereology and Allergology
contact email	schmidt_M11@ukw.de
lab head
Marc Schmidt
contact affiliation	University Hospital Wuerzburg, Department of Dermatology, Venereology and Allergology
contact email	schmidt_M11@ukw.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/01/PXD027615

PRIDE project URI

• PRIDE
  1. PXD027615
     1. Label: PRIDE project
     2. Name: HUVEC 3xHA.FoxO3.A3.ER +4-OHT vs vector +4-OHT