PXD037623

PXD037623 is an original dataset announced via ProteomeXchange.

Title	The RNA Binding Protein IGF2BP2 is Upregulated by Stress in the Heart and Causes Mitochondrial Dysfunction and Dilated Cardiomyopathy
Description	The IGF2BP family of RNA binding proteins consists of three paralogs, IGF2BP1, 2, and 3, that regulate RNA function at many levels, including intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. Several previous studies indicated that IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodelling and returns to normal levels in recovering hearts. These results suggested that IGF2BP2 might play an adaptive role during cardiac stress and recovery. To investigate the role of IGF2BP2 in the heart, we made use of a conditional, inducible transgenic mouse line. Enhanced expression of the IGF2BP2 transgene in hearts of newborn or adult mice leads to dilated cardiomyopathy (DCM), with remodelling, fibrosis, and death occurring within 3-4 weeks. Turning off expression of the transgene after 2 weeks, however, rescues these mice, and they recover completely by 12 weeks. Proteomic analysis identified a downregulation of sarcomeric and mitochondrial proteins in hearts overexpressing IGF2BP2, and electron microscopy revealed fragmented mitochondria and elongated, thinner sarcomeres, suggesting a possible mechanism of action. Consistent with these results, IGF2BP2 is upregulated in patients with DCM or after myocardial infarction. These results show that cardiac stress upregulates IGF2BP2, and this upregulation causes remodelling and compensation of the heart. Prolonged IGF2BP2 expression, however, leads to heart failure and death, making it an attractive target for therapeutic intervention.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:25:09.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hanan Schoffman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-20 13:35:43	ID requested
1	2024-01-26 06:13:19	announced
⏵ 2	2024-10-22 06:25:11	announced	2024-10-22: Updated project metadata.

Krumbein M, Oberman F, Cinnamon Y, Golomb M, May D, Vainer G, Belzer V, Meir K, Fridman I, Haybaeck J, Poelzl G, Kehat I, Beeri R, Kessler SM, Yisraeli JK, RNA binding protein IGF2BP2 expression is induced by stress in the heart and mediates dilated cardiomyopathy. Commun Biol, 6(1):1229(2023) [pubmed]

10.1038/s42003-023-05547-x;

submitter keyword: heart,Mouse, LCMS, IGF2BP2

Joel K. Yisraeli
contact affiliation	Department of Developmental Biology and Cancer Research,Hebrew University of Jerusalem, Israel
contact email	joel.yisraeli@mail.huji.ac.il
lab head
Hanan Schoffman
contact affiliation	The Hebrew University of Jerusalem
contact email	Hanan.schoffman@mail.huji.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037623
     1. Label: PRIDE project
     2. Name: The RNA Binding Protein IGF2BP2 is Upregulated by Stress in the Heart and Causes Mitochondrial Dysfunction and Dilated Cardiomyopathy