PXD024088

PXD024088 is an original dataset announced via ProteomeXchange.

Title	Neddylation modification on cGAS of human and mouse
Description	The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthetase (cGAS) has emerged as a fundamental component fueling the anti-pathogen immunity. Because of its pivotal role in initiating innate immune response, the activity of cGAS must be tightly fine-tuned to maintain immune homeostasis in antiviral response. Here, we reported that neddylation modification was indispensable for appropriate cGAS-STING signaling activation. Blocking neddylation pathway using neddylation inhibitor MLN4924 substantially impaired the induction of type I interferon and proinflammatory cytokines, which was selectively dependent on Nedd8 E2 enzyme Ube2m. We further found that deficiency of the Nedd8 E3 ligase Rnf111 greatly attenuated DNA-triggered cGAS activation while not affecting cGAMP induced activation of STING, demonstrating that Rnf111 was the Nedd8 E3 ligase of cGAS. We further identified Lys231 and Lys421 as the key neddylation sites in human cGAS. Mechanistically, Rnf111 interacted with and polyneddylated cGAS, which in turn promoted its dimerization and enhanced the DNA-binding ability, leading to proper cGAS-STING pathway activation. In the same line, the Ube2m or Rnf111 deficiency mice exhibited severe defects in innate immune response and were susceptible to HSV-1 infection. Collectively, our study uncovered a vital role of the Ube2m-Rnf111 neddylation axis in promoting the activity of the cGAS-STING pathway and highlighted the importance of neddylation modification in antiviral defense.
HostingRepository	PRIDE
AnnounceDate	2021-02-22
AnnouncementXML	Submission_2021-02-21_22:50:45.988.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haiyang Hu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-09 08:57:43	ID requested
⏵ 1	2021-02-21 22:50:46	announced

Dataset with its publication pending

submitter keyword: Neddylation, human, mouse, cGAS

Haiyang Hu
contact affiliation	China Pharmaceutical University
contact email	haiyanghu@cpu.edu.cn
lab head
Haiyang Hu
contact affiliation	China Pharmaceutical University
contact email	haiyanghu@cpu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024088
     1. Label: PRIDE project
     2. Name: Neddylation modification on cGAS of human and mouse