PXD046677

PXD046677 is an original dataset announced via ProteomeXchange.

Title	Small molecule induced STING degradation facilitated by the HECT ligase HERC4
Description	Stimulator of interferon genes (STING) is a central component of the cytosolic nucleic acids sensing pathway and as such master regulator of the type I interferon response. Due to its critical role in physiology and its’ involvement in a variety of diseases, STING has been a focus for drug discovery. Targeted protein degradation (TPD) has emerged as a promising pharmacology for targeting previously considered undruggable proteins by hijacking the cellular ubiquitin proteasome system (UPS) with small molecules. Here, we identify AK59 as a STING degrader leveraging HERC4, a HECT-domain E3 ligase. Additionally, our data reveals that AK59 is effective on the common pathological STING mutations, suggesting a potential clinical application of this mechanism. Thus, these findings introduce HERC4 to the field of TPD and a compound-induced degradation of STING, suggesting potential therapeutic applications.
HostingRepository	PRIDE
AnnounceDate	2024-04-12
AnnouncementXML	Submission_2024-04-12_04:11:01.675.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD046677
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Andreas Hofmann
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-05 06:55:42	ID requested
⏵ 1	2024-04-12 04:11:02	announced

10.6019/PXD046677;

submitter keyword: targeted protein degradation, HERC4, TMT, MGD, glue degrader, TPD,STING

Andreas Josef
contact affiliation	Biomedical Research, Novartis Pharma AG
contact email	andreas.hofmann@novartis.com
lab head
Andreas Hofmann
contact affiliation	NIBR
contact email	andreas.hofmann@novartis.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046677
     1. Label: PRIDE project
     2. Name: Small molecule induced STING degradation facilitated by the HECT ligase HERC4