PXD019359

PXD019359 is an original dataset announced via ProteomeXchange.

Title	cGAS Senses Translation Stress Through Direct Binding to Ribosomes
Description	The cGAS-STING pathway, a central component of the innate immune system, senses cytosolic DNA and induces interferon-stimulated genes (ISGs) to mediate inflammation. Here we report the unexpected discovery that cGAS senses dysfunctional protein production. Purified ribosomes interact with and stimulate the catalytic activity of recombinant cGAS in vitro. Disruption of the ribosome-associated protein quality control pathway, which detects and resolves ribosome collisions, results in cGAS- and STING-dependent ISG expression, and causes the re-localization of cGAS from the nucleus to the cytosol. Indeed, cGAS preferentially binds collided ribosomes in vitro, and other orthogonal perturbations that lead to elevated levels of collided ribosomes cause re-localization of cGAS as well. Thus, the cGAS-STING pathway senses and responds to translation stress. These findings have implications for the inflammatory responses to viral infection and tumorigenesis, both of which substantially reprogram cellular protein synthesis.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-08_19:11:26.842.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Faull
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-24 23:05:46	ID requested
⏵ 1	2021-09-08 19:11:27	announced

Wan L, Juszkiewicz S, Blears D, Bajpe PK, Han Z, Faull P, Mitter R, Stewart A, Snijders AP, Hegde RS, Svejstrup JQ, Translation stress and collided ribosomes are co-activators of cGAS. Mol Cell, 81(13):2808-2822.e10(2021) [pubmed]

submitter keyword: cGAS, ribosomes, ASCC, human

Bram Snijders
contact affiliation	Head of the Crick Mass Spectrometry Proteomics Platform
contact email	bram.snijders@crick.ac.uk
lab head
Peter Faull
contact affiliation	The Francis Crick Institute
contact email	peter.faull@crick.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/2021/09/PXD019359

PRIDE project URI

• PRIDE
  1. PXD019359
     1. Label: PRIDE project
     2. Name: cGAS Senses Translation Stress Through Direct Binding to Ribosomes