PXD043560-2

PXD043560 is an original dataset announced via ProteomeXchange.

Title	A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death
Description	Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that co- ordinates cell survival, inflammation, and immunogenic cell death (ICD). Although the catalytic function of RIPK1 is required to trigger cell death, its non-catalytic scaffold function mediates strong pro-survival signaling. Accordingly, cancer cells can hijack RIPK1 to block necroptosis and evade immune detection. We generated a small-molecule proteolysis-targeting chimera (PROTAC) that selectively degraded human and murine RIPK1. PROTAC-mediated depletion of RIPK1 deregulated TNFR1 and TLR3/4 signaling hubs, accentuating the output of NF-kB, MAPK, and IFN signaling. Additionally, RIPK1 degradation simultaneously promoted RIPK3 activation and necroptosis induction. We further demonstrated that RIPK1 degradation enhanced the immunostimulatory effects of radio- and immunotherapy by sensitizing cancer cells to treat- ment-induced TNF and interferons. This promoted ICD, antitumor immunity, and durable treatment responses. Consequently, targeting RIPK1 by PROTACs emerges as a promising approach to overcome radio- or immunotherapy resistance and enhance anticancer therapies.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:41:57.160.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Graeme Benstead-Hume
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-05 08:20:32	ID requested
1	2024-05-23 07:28:51	announced
⏵ 2	2024-10-22 06:41:57	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: inflammation,RIPK1, PROTAC

Jyoti Choudhary
contact affiliation	Functional Proteomics, ICR
contact email	jyoti.choudhary@icr.ac.uk
lab head
Graeme Benstead-Hume
contact affiliation	ICR
contact email	ghume@icr.ac.uk
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/2024/05/PXD043560

PRIDE project URI

• PRIDE
  1. PXD043560
     1. Label: PRIDE project
     2. Name: A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death