Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ErbB2 drives Yap activation during cardiac regeneration

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart

DISEASE(S): Myocardial Ischemia

SUBMITTER: Alon Savidor

LAB HEAD: Eldad Tzahor

PROVIDER: PXD020731 | Pride | 2020-08-21

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	F007626_PG1_1_F2.dat	Other
	F007631_PG1_1_F3.dat	Other
	F007632_PG1_1_F4.dat	Other
	F007637_PG1_1_F5.dat	Other
	F007639_PG1_1_F6.dat	Other

Items per page:

1 - 5 of 283

Similar Datasets

Arabidopsis leaf senescence

Project description:Monitor changes in the proteome of senescing leaves, using protein MS data obtained from the same leaf groups used for imaging. Arabidopsis thaliana mature leaves were grouped according to their chlorophyll content: Dark Green (DG), Green (G), Light Green (LG) and Yellow (Y), containing 100, 45, 25 and 6.5% chlorophyll relative to DG, respectivelyArabidopsis thaliana mature leaves were grouped according to their chlorophyll content: Dark Green (DG), Green (G), Light Green (LG) and Yellow (Y), containing 100, 45, 25 and 6.5% chlorophyll relative to DG, respectively

2022-03-02 | PXD010465 | Pride

Redifferentiated cardiomyocytes retain residual dedifferentiation signatures and are protected against ischaemic injury

Project description:Near-complete reversal of ERBB2-driven cardiomyocyte dedifferentiation is driven by the Hippo pathway, restoring contractility whilst long-lasting conferring cardioprotection.

2023-02-01 | PXD038450 | Pride

YAP transcriptionally regulates ErbB2 to promote liver cell proliferation

Project description:The Hippo signaling pathway is implicated in regulation of liver size and dysregulation of this pathway contributes to tumorigenesis. The transcriptional targets and downstream pathways of the Hippo pathway effector YAP that contribute to liver growth have yet to be well-characterized. We examined the liver transcriptome in response to YAP overexpression and identify the ErbB signaling pathway as a mediator of cell growth downstream of YAP. ErbB2 is transcriptionally regulated by YAP in both the mouse liver and in HepG2 human hepatoma cells. Knockdown of YAP or pharmacological inhibition with verteporfin reduced ERBB2 levels in HepG2 cells. Analysis of ChIP-seq data revealed enrichment of the transcription factor TEAD4 at the ERBB2 promoter. Using luciferase reporter and chromatin immunoprecipitation assays, we show that YAP and TEAD directly bind to and activate a regulatory element in the ErbB2 promoter in both the mouse liver and HepG2 cells. Functionally, knockdown of YAP reduced EGF-induced ERBB2-mediated HepG2 cell proliferation and PI3K/AKT activation. Our findings highlight a mechanism by which YAP exerts its effects on liver cell proliferation through the ErbB signaling pathway by directly regulating the transcription of ErbB2.

2018-02-09 | GSE110383 | GEO

Site-specific glycan analysis of ErbB2 in breast cancer cell SKBR-3

2024-05-24 | PXD039837 | Pride

Site-specific glycan analysis of epidermal growth factor receptor 2

Project description:This study provides site-specific profiles of asparagine-linked and serine/threonine-linked glycosylations on ErbB2, a therapeutic target RTK for ErbB2-positive cancer, through structural analysis of recombinant ErbB2 extracellular region and endogenous ErbB2 from ErbB2-positive breast cancer cells. Furthermore, comparison of the N-glycosylated structures of the extracellular regions of ErbB2 and its homologue, the epidermal growth factor receptor (EGFR), showed differences in the distribution and density of N-glycans on both molecules, providing new insights into the different activation mechanisms of ErbB2 and EGFR from a glycan perspective.

2024-05-21 | PXD039834 | Pride

Site-specific glycan analysis of CHO cell expressed epidermal growth factor receptor 2

2024-05-21 | PXD039835 | Pride

Homo sapiens

Project description:MCF10A YAP-OE RNA-seq analysis

| PRJNA288903 | ENA

YAP transcriptionally regulates ErbB2 to promote liver cell proliferation

Project description:YAP transcriptionally regulates ErbB2 to promote liver cell proliferation

| PRJNA433574 | ENA

YAP Partially Reprograms Chromatin Accessibility to Directly Induce Adult Cardiogenesis in Vivo

Project description:Specialized adult somatic cells, such as cardiomyocytes (CMs), are highly differentiated with poor renewal capacity, an integral reason underlying organ failure in disease and aging. Among the least renewable cells in the human body, CMs renew approximately 1% annually. Consistent with poor CM turnover, heart failure is the leading cause of death. Here, we show that an active version of the Hippo pathway effector YAP, termed YAP5SA, partially reprograms adult mouse CMs to a more fetal and proliferative state. One week after induction, 19% of CMs that enter S-phase do so twice, CM number increases by 40%, and YAP5SA lineage CMs couple to pre-existing CMs. Genomic studies showed that YAP5SA increases chromatin accessibility and expression of fetal genes, partially reprogramming long-lived somatic cells in vivo to a primitive, fetal-like, and proliferative state.

2019-02-14 | GSE123457 | GEO

YAP promotes cardiomyocyte cell cycle entry

2024-01-11 | GSE152856 | GEO