Dataset Information

Identification of cGAS post-translational modifications

ABSTRACT: 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.

ORGANISM(S): Homo Sapiens

SUBMITTER: Todd Greco

PROVIDER: PXD017133 | panorama | Fri May 08 00:00:00 BST 2020

REPOSITORIES: PanoramaPublic

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Publications

The DNA Sensor cGAS is Decorated by Acetylation and Phosphorylation Modifications in the Context of Immune Signaling.

Song Bokai B Greco Todd M TM Lum Krystal K KK Taber Caroline E CE Cristea Ileana M IM

Molecular & cellular proteomics : MCP 20200428 7

The cyclic GMP-AMP synthase (cGAS) protein is a pattern-recognition receptor of the mammalian innate immune system that is recognized as a main cytosolic sensor of pathogenic or damaged DNA. cGAS DNA binding initiates catalytic production of the second messenger, cyclic GMP-AMP, which activates the STING-TBK1-IRF3 signaling axis to induce cytokine expression. Post-translational modification (PTM) has started to be recognized as a critical component of cGAS regulation, yet the extent of these mod ...[more]

PMID: 32345711

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Dataset Information

Identification of cGAS post-translational modifications

Publications

The DNA Sensor cGAS is Decorated by Acetylation and Phosphorylation Modifications in the Context of Immune Signaling.

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