PXD063855

PXD063855 is an original dataset announced via ProteomeXchange.

Title	The Kinase CK1a coordinates Initiation and Termination of the cGAS-STING Pathway
Description	The cGAS-STING pathway is an evolutionarily conserved antimicrobial defense mechanism that senses cytosolic DNA to trigger innate immune responses. cGAS and STING play dual roles in tumorigenesis, promoting antitumor immunity and cell death while fueling tumor growth and metastasis. However, the mechanisms fine-tuning this pathway remain elusive. Using unbiased proteomic approaches, we report that Casein Kinase 1 alpha (CK1α) operates as a bimodal regulator of the cGAS-STING pathway. CK1α supports optimal DNA sensing by preventing the proteasomal degradation of cGAS driven by the cullin-RING ubiquitin ligase 3 (CRL3). Conversely, CK1α facilitates STING degradation and signaling termination in response to STING agonists, tempering IRF3 activation. Exploiting these counterposing functions, we show that selective degradation of CK1α with molecular-glue degraders impaired the survival of a triple-negative breast cancer cell line with chronic cGAS-STING activation and synergized with a STING agonist to kill acute myeloid leukemia cells. Thus, CK1α’s dual regulatory role in the cGAS-STING pathway presents a promising target for therapeutic development.
HostingRepository	PRIDE
AnnounceDate	2026-09-10
AnnouncementXML	Submission_2026-09-10_07:13:34.973.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François Guillonneau
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-12 07:32:27	ID requested
⏵ 1	2026-09-10 07:13:35	announced

10.1038/s41418-026-01844-0;

Jardine J, Tarrillon M, Andr, é, -Gr, é, goire G, Trillet K, Josso V, Merlet L, Moreau R, Jaunasse C, Antigny L, Marionneau-Lambot S, Guillonneau F, Boissard A, Henry C, Re J, Barill, é, -Nion S, Laguette N, Juin PP, Gavard J, Bid, è, re N, coordinates the initiation and termination of the cGAS-STING pathway. Cell Death Differ, ():(2026) [pubmed]

submitter keyword: Biotin, APEX, LC-MS, cGAS/ting,AP-MS, CK1-alpha

Nicolas Bidere
contact affiliation	Team SOAP, CRCI2NA, Nantes University, INSERM, CNRS, Université d'Angers, Nantes, France. Equipe Labellisée Ligue Contre le Cancer, Nantes
contact email	nicolas.bidere@inserm.fr
lab head
François Guillonneau
contact affiliation	Institut de Cancerologie de l'Ouest (ICO) Angers
contact email	francois.guillonneau@inserm.fr
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/2026/09/PXD063855

PRIDE project URI

• PRIDE
  1. PXD063855
     1. Label: PRIDE project
     2. Name: The Kinase CK1a coordinates Initiation and Termination of the cGAS-STING Pathway