PXD028918-2

PXD028918 is an original dataset announced via ProteomeXchange.

Title	FAT10 is phosphorylated by IKKβ to inhibit the antiviral type-I interferon response
Description	Type-I interferon (IFN-I) secretion provides a rapid host defense against infection with RNA-viruses. Upon entry into the host cell, the viral RNA triggers the activation of both RIG-I and TLR3 signaling pathways, ultimately leading to the production of type-I interferons. Since an exaggerated IFNa/b response can cause severe tissue damage, these pathways are tightly regulated. One of the factors that keep the type 1 IFN response in check is the ubiquitin-like modifier FAT10. FAT10 is expressed upon synergistic stimulation with TNFα and IFNγ, and it targets covalently FAT10-linked substrate proteins for proteasomal degradation. However, the mechanism how FAT10 modulates IFN-I secretion remains to be fully elucidated. Here, we found that FAT10 is phosphorylated by Ikb kinase b (IKKβ) upon TNFα stimulation and during Influenza Virus infection on several serine and threonine residues. FAT10 phosphorylation increases the binding of FAT10 to the TRAF3-deubiquitylase OTUB1 and its FAT10-mediated activation. Consistently, FAT10 phosphorylation results in a low ubiquitylation state of TRAF3 which is unable to maintain IRF3 phosphorylation and downstream induction of type 1 IFNs. Taken together, we reveal a mechanism how the TNF-induced phosphorylation of FAT10 limits the production of tissue destructive IFN-I in inflammation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:16:30.660.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivan Silbern
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-04 10:00:44	ID requested
1	2023-11-07 03:44:35	announced
⏵ 2	2023-11-14 08:16:31	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:13:47	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: FAT10, Ubiquitin D, UBD, Phosphorylation

Prof. Dr. Henning Urlaub
contact affiliation	Max-Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany University Clinical Center Goettingen, 37075 Goettingen, Germany
contact email	henning.urlaub@mpibpc.mpg.de
lab head
Ivan Silbern
contact affiliation	MPI Biophysical Chemistry
contact email	ivansilbern@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028918
     1. Label: PRIDE project
     2. Name: FAT10 is phosphorylated by IKKβ to inhibit the antiviral type-I interferon response