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PXD030594-1

PXD030594 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIntercepting IRE1 Kinase-FMRP Signaling Prevents Atherosclerosis Progression
DescriptionFragile X Mental Retardation protein (FMRP), widely known for its role in hereditary intellectual disability, is an RNA-binding protein (RBP) that controls translation of select mRNAs. We discovered that endoplasmic reticulum (ER) stress induces phosphorylation of FMRP on a site that is known to enhance translation inhibition of FMRP-bound mRNAs. We show ER stress-induced activation of Inositol requiring enzyme-1 (IRE1), an ER-resident stress-sensing kinase/endoribonuclease, leads to FMRP phosphorylation and to suppression of macrophage cholesterol efflux and apoptotic cell clearance (efferocytosis). Conversely, FMRP-deficiency and pharmacological inhibition of IRE1 kinase activity enhances cholesterol efflux and efferocytosis, reducing atherosclerosis in mice. Our results provide mechanistic insights into how ER stress-induced IRE1 kinase activity contributes to macrophage cholesterol homeostasis and suggest IRE1 inhibition as a promising new way to counteract atherosclerosis.
HostingRepositoryPRIDE
AnnounceDate2022-02-15
AnnouncementXMLSubmission_2022-02-15_01:57:09.660.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD030594
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterSabyasachi Baboo
SpeciesList scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-12-22 02:37:07ID requested
12022-02-15 01:57:10announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Kinase-substrate, translational regulation, cholesterol homeostasis, efferocytosis, atherosclerosis
Contact List
John R Yates III
contact affiliationThe Scripps Research Institute, Department of Molecular Medicine, La Jolla, California, USA
contact emailjyates@scripps.edu
lab head
Sabyasachi Baboo
contact affiliationThe Scripps Research Institute, La Jolla, California
contact emailsbaboo@scripps.edu
dataset submitter
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Dataset FTP location
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