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PXD037697

PXD037697 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFAM69C functions as a kinase for eIF2α and promotes stress granule assembly
DescriptionStress 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_06:49:28.856.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFan Mei
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-10-25 04:31:59ID requested
12023-04-21 05:28:03announced
22023-11-14 06:49:29announced2023-11-14: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: eIF2α
FAM69C
inflammasome
stress response
stress granule.
Contact List
Fan Mei
contact affiliationInstitute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
contact emailmeifan@hsc.pku.edu.cn
lab head
Fan Mei
contact affiliationPeking University
contact emailmeifan@hsc.pku.edu.cn
dataset submitter
Full Dataset Link List
Dataset FTP location
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