PXD020731-1

PXD020731 is an original dataset announced via ProteomeXchange.

Title	ErbB2 drives Yap activation during cardiac regeneration
Description	Cardiomyocyte (CM) loss after injury results in adverse remodelling and fibrosis, which inevitably lead to heart failure. Neuregulin-ErbB2 and Hippo-Yap signaling pathways are key mediators of CM proliferation and regeneration although the crosstalk between these pathways is unclear. Here, we demonstrate in mice that temporal over-expression (OE) of activated ErbB2 in CMs promotes cardiac regeneration in a heart failure model. Cellularly, OE CMs present an EMT-like regenerative response involving cytoskeletal reprograming, migration, ECM turnover, and displacement. Molecularly, we identified Yap as a critical mediator of ErbB2 signaling. In OE CMs, Yap interacts with nuclear envelope and cytoskeletal components, reflective of the altered mechanic state elicited by ErbB2. Hippo-independent activating phosphorylation on Yap at S352 and S274 were enriched in OE CMs, peaking during metaphase. Viral overexpression of Yap phospho-mutants dampened the proliferative competence of OE CMs. Taken together, we demonstrate a potent ErbB2-mediated Yap mechanosensory signaling involving EMT-like characteristics, resulting in heart regeneration.
HostingRepository	PRIDE
AnnounceDate	2020-08-21
AnnouncementXML	Submission_2020-08-21_06:17:39.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alon Savidor
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-05 02:56:07	ID requested
⏵ 1	2020-08-21 06:17:39	announced

Dataset with its publication pending

submitter keyword: LFQ, DDA, phosphoproteomics, mouse, orbitrap, IP

Eldad Tzahor
contact affiliation	Department of Molecular Cell Biology Weizmann Institute of Science
contact email	eldad.tzahor@weizmann.ac.il
lab head
Alon Savidor
contact affiliation	The Weizmann Institute of Science
contact email	alon.savidor@weizmann.ac.il
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020731
     1. Label: PRIDE project
     2. Name: ErbB2 drives Yap activation during cardiac regeneration