PXD043331

PXD043331 is an original dataset announced via ProteomeXchange.

Title	ESCRT regulates the termination of STING activity by mediating its degradation
Description	STING is a key signaling hub in pathogen defense response. The understanding of STING turnover in lysosomes remains superficial. Here, combining APEX- and Tandem Affinity Purification-based unbiased mass spectrometry screens, we identified ESCRT proteins that interact with STING. Further experimental characterization shows that these ESCRT machineries are required for both termination of STING activity and STING degradation in both its activated and steady states, and that the required ESCRT proteins differ between mice and humans. Upon activation, STING interacts with ESCRT proteins, leading to its lysosomal degradation. Furthermore, STING degradation is ubiquitin-independent, and requires binding between the STING cytoplasmic loop region and the TSG101 SB domain. Mutations in this loop disrupt their interaction, inhibiting STING degradation and consequently maintaining STING activation. In vitro synthesized peptides mimicking the cytoplasmic loop can disrupt STING-TSG101 interaction, inhibiting its STING degradation and activity termination. Notably, pre-treatment with loop mimic peptides can also attenuate HSV-1 proliferation in vitro. This study describes a previously unrecognized ESCRT-dependent, ubiquitin-independent mechanism underlying STING degradation and activity termination and suggests the further exploration of synthetic peptides that mediate targeted disruption of ESCRT-STING interactions as a therapeutic strategy for treating infectious diseases via prolonged STING activation.
HostingRepository	iProX
AnnounceDate	2023-06-27
AnnouncementXML	Submission_2023-06-27_00:24:11.751.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haohao Tang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-06-27 00:23:50	ID requested
⏵ 1	2023-06-27 00:24:12	announced

Dataset with its publication pending

submitter keyword: STING, ESCRT

Yang Chen
contact affiliation	Peking University Health Science Center
contact email	chenyang1816185048@bjmu.edu.cn
lab head
Haohao Tang
contact affiliation	Peking University Health Science Center
contact email	Tanghaohao0987@163.com
dataset submitter

iProX dataset URI