PXD030594-1

PXD030594 is an original dataset announced via ProteomeXchange.

Title	Intercepting IRE1 Kinase-FMRP Signaling Prevents Atherosclerosis Progression
Description	Fragile 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.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_01:57:09.660.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD030594
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sabyasachi Baboo
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-22 02:37:07	ID requested
⏵ 1	2022-02-15 01:57:10	announced

Dataset with its publication pending

submitter keyword: Kinase-substrate, translational regulation, cholesterol homeostasis, efferocytosis, atherosclerosis

John R Yates III
contact affiliation	The Scripps Research Institute, Department of Molecular Medicine, La Jolla, California, USA
contact email	jyates@scripps.edu
lab head
Sabyasachi Baboo
contact affiliation	The Scripps Research Institute, La Jolla, California
contact email	sbaboo@scripps.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030594
     1. Label: PRIDE project
     2. Name: Intercepting IRE1 Kinase-FMRP Signaling Prevents Atherosclerosis Progression