PXD017133

PXD017133 is an original dataset announced via ProteomeXchange.

Title	Identification of cGAS post-translational modifications
Description	DNA derived from the genetic material of pathogens or from cellular DNA damage provides a molecular pattern that can be sensed by pattern-recognition receptors of the mammalian innate immune system. In recent years, the cyclic GMP-AMP synthase (cGAS) protein has been characterized as a primary cytosolic DNA sensor during infection with bacteria, DNA viruses, or retroviruses. While the role of cGAS in downstream immune signaling through STING-TBK1-IRF3 proteins is well-defined, regulatory mechanisms of cGAS activity, such as through post-translational modifications (PTMs), are still an active area of research. Here, we report a comprehensive characterization of cGAS phosphorylations and acetylations in multiple cell types, HEK293T, primary human fibroblast, and THP-1 cells. A total of 11 PTMs (4 phosphorylations and 7 acetylations) were validated through a combination of data-dependent proteomic analysis and parallel reaction monitoring targeted MS on immunoaffinity purified cGAS. Of these, 3 phosphorylations and 5 acetylations have not been previously identified. The functions of these modifications were investigated by generating a series of mutants and measuring cGAS-dependent apoptotic and immune signaling activities.
HostingRepository	PanoramaPublic
AnnounceDate	2020-05-08
AnnouncementXML	Submission_2020-05-08_13:57:03.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Todd Greco
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	Phospho; Acetyl; Carbamidomethyl
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-15 23:35:19	ID requested
⏵ 1	2020-05-08 13:57:05	announced

Song B, Greco TM, Lum KK, Taber CE, Cristea IM, The DNA Sensor cGAS is Decorated by Acetylation and Phosphorylation Modifications in the Context of Immune Signaling. Mol Cell Proteomics, 19(7):1193-1208(2020) [pubmed]

submitter keyword: phosphorylation, acetylation, immune response, herpesvirus, IP-MS

Ileana Cristea
contact affiliation	Princeton University
contact email	icristea@princeton.edu
lab head
Todd Greco
contact affiliation	Princeton University
contact email	tgreco@princeton.edu
dataset submitter

Panorama Public dataset URI