PXD017109

PXD017109 is an original dataset announced via ProteomeXchange.

Title	Identification of cGAS acetylation and phosphorylation
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 three different cell types. Data-dependent proteomic analyses of immunoaffinity purified cGAS was performed in HEK293T cells under control and DNA-challenged conditions (N = 3 each) and human fibroblasts (HFF) cells under control and HSV-1 infected conditions (N = 4 each) to generate candidate cGAS PTM sites. Using parallel reaction monitoring, a total of 11 PTMs (4 phosphorylations and 7 acetylations) were validated in HEK293T, HFF, and THP-1 cells. Of these, 3 phosphorylations and 5 acetylations have not been previously identified. The functions of these modifications were by generating a series of mutants and measuring cGAS-dependent apoptotic and immune signaling activities.
HostingRepository	PRIDE
AnnounceDate	2020-05-11
AnnouncementXML	Submission_2020-05-10_22:21:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	T Greco
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-15 02:28:57	ID requested
⏵ 1	2020-05-10 22:21:50	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: Human, immune response, herpesvirus, PTM, affinity purification

Ileana M Cristea
contact affiliation	Department of Molecular Biology, Princeton University, USA
contact email	icristea@princeton.edu
lab head
T Greco
contact affiliation	Molecular Biology
contact email	tgreco@princeton.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017109
     1. Label: PRIDE project
     2. Name: Identification of cGAS acetylation and phosphorylation