PXD029215

PXD029215 is an original dataset announced via ProteomeXchange.

Title	LC-MS of FLAG-tagged C-terminal domain of human DUX4
Description	DUX4 activates the first wave of zygotic gene expression in the early embryo. Mis-expression of DUX4 in skeletal muscle causes facioscapulohumeral dystrophy (FSHD), whereas expression in cancers suppresses IFNg-induction of MHC Class I and contributes to immune evasion. We show that the DUX4 protein broadly suppresses immune signaling pathways—including IFNg, IFNb, DDX58, IFIH1 and cGAS mediated pathways. A conserved region containing (L)LxxL(L) motifs in the DUX4 carboxyterminal domain (CTD) was necessary to suppress interferon stimulated genes (ISGs). Co-immunoprecipitation identified DUX4-CTD interaction with multiple immune signaling factors, including STAT1. The DUX4-CTD (L)LxxL(L) region interacts with phosphorylated STAT1, sequesters it in the nucleus, modestly reduces its DNA binding, and prevents STAT1 from inducing ISG transcription. Mouse Dux similarly interacted with STAT1 and suppressed IFNg induction of ISGs. These findings identify an evolved role of the DUXC family in modulating immune signaling pathways with implications for development, cancers, and FSHD.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:41.240.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sean Bennett
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-19 01:48:20	ID requested
1	2023-05-10 10:59:19	announced
⏵ 2	2023-11-14 08:53:41	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: interferon gamma, cGAS, DUX, interferon beta, RIG-I,DUX4, MDA5, STAT1, DUXC, interferon stimulated genes

Stephen J. Tapscott
contact affiliation	Human Biology Division, Fred Hutchinson Research Center, Seattle, WA, USA.
contact email	sjtapscot@fredhutch.org
lab head
Sean Bennett
contact affiliation	Fred Hutchinson Cancer Research Center
contact email	srbennet@fredhutch.org
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/2023/05/PXD029215

PRIDE project URI

• PRIDE
  1. PXD029215
     1. Label: PRIDE project
     2. Name: LC-MS of FLAG-tagged C-terminal domain of human DUX4