PXD037697

PXD037697 is an original dataset announced via ProteomeXchange.

Title	FAM69C functions as a kinase for eIF2α and promotes stress granule assembly
Description	Stress granules are dynamic cytoplasmic ribonucleoprotein granules that assemble in response to cellular stress. Aberrant formation of stress granules has been linked to neurodegenerative diseases. However, the molecular mechanisms underlying the initiation of stress granules remain elusive. Here we report that the brain-enriched protein kinase FAM69C promotes stress granule assembly through phosphorylation of eukaryotic translation initiation factor 2 (eIF2α). FAM69C physically interacts with eIF2α and functions as a stress-specific kinase for eIF2α, leading to stress-induced protein translation arrest and stress granule assembly. Primary microglia derived from Fam69c knockout mice exhibit aberrant stress granule assembly in response to oxidative stress and ATP. Defective stress granule assembly in microglia correlates with the formation of ASC specks and NLRP3 inflammasome activation, whereas induction of stress granule precludes inflammasome formation. Consistently, increased NLRP3 levels, caspase-1 cleavage and Il18 expression corroborate microglia-associated neuroinflammation in aged Fam69c knockout mice. Our study demonstrates that FAM69C is critical for stress granule assembly and suggests its role in the regulation of microglia function.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_06:49:28.856.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fan Mei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-25 04:31:59	ID requested
1	2023-04-21 05:28:03	announced
⏵ 2	2023-11-14 06:49:29	announced	2023-11-14: Updated project metadata.

Wu Z, Mei F, Gan Y, Liu A, Hu J, Jin Y, Yin Y, and promotes stress granule assembly. EMBO Rep, 24(5):e55641(2023) [pubmed]

submitter keyword: eIF2α

FAM69C

inflammasome

stress response

stress granule.

Fan Mei
contact affiliation	Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
contact email	meifan@hsc.pku.edu.cn
lab head
Fan Mei
contact affiliation	Peking University
contact email	meifan@hsc.pku.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037697
     1. Label: PRIDE project
     2. Name: FAM69C functions as a kinase for eIF2α and promotes stress granule assembly