PXD045603-1

PXD045603 is an original dataset announced via ProteomeXchange.

Title	STING induces LUBAC synthesis of linear ubiquitin chains to activate NFkB
Description	STING activation by cyclic dinucleotides in mammals induces Type I Interferon- and NFkB-related gene expression, and the lipidation of LC3B at Golgi membranes. While the mechanisms of the Interferon-related responses are well understood, the mechanism of NFkB activation mediated by STING activation, and how the multi-functional responses downstream of STING signaling are related remain unknown. We report that STING activation induces K63 and linear ubiquitin chain formation, and ubiquitin co-localizes with STING and LC3B at Golgi-derived vesicles. Loss of the LUBAC E3 ubiquitin ligase subunit, HOIP, prevents formation of the linear, but not K63-linked, ubiquitin chains. The ubiquitin and LC3B binding proteins, Optineurin and TNIP1, are co-localized with STING activation-induced, perinuclear LC3B foci via their UBAN domains, however loss of HOIP does not influence this localization, indicating they may bind the K63-linked ubiquitin chains. HOIP-mediated linear ubiquitin chains are well established to mediate NFkB downstream of TNFa and IL1beta receptor stimulation. Loss of HOIP in monocytic THP-1 cells inhibits STING-induced NFkB activation and NFkB-related gene transcription, as well as Interferon-related transcription. Further, the recently reported proton channel activity of STING that blocks LC3B lipidation at Golgi membranes is also important for both K63 and Linear ubiquitin chain formation, and NFkB signaling. Thus, STING induces HOIP and linear ubiquitin chain formation to activate NFkB.
HostingRepository	MassIVE
AnnounceDate	2024-10-18
AnnouncementXML	Submission_2024-10-18_07:03:02.427.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yan Wang
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	GG
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-22 12:54:39	ID requested
⏵ 1	2024-10-18 07:03:02	announced

no publication

submitter keyword: STING activation, linear, K48, K63 polyubiqitin chains, NFkB signaling

Yan Wang
contact affiliation	NIH/NIDCR
contact email	wangyan2@nih.gov
lab head
Yan Wang
contact affiliation	NIH
contact email	yan.wang2@nih.gov
dataset submitter

MassIVE dataset URI

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