PXD020843

PXD020843 is an original dataset announced via ProteomeXchange.

Title	The E3 ubiquitin ligase HectD3 is a novel regulator of cardiac hypertrophy and inflammation
Description	The HECT domain E3 ubiquitin protein ligase 3 (HectD3) is highly expressed in the heart, but its cardiac function is still unknown. Here, we identified SUMO2 and Stat1 as novel cardiac substrates for HectD3. SUMO2 is a potent inducer of Calcineurin-NFAT mediated cardiomyocyte hypertrophy, whereas, Stat1 is an interferon responsive transcription factor that plays crucial role in cellular immune responses. HectD3 overexpression on one hand attenuated SUMO2-Calcineurin-NFAT signaling driven cardiomyocyte hypertrophy, on the other hand, it abrogated the pro-inflammatory actions of LPS or interferon-γ in cardiomyocytes in vitro. Consistently, AAV9-mediated overexpression of HectD3 in mice in vivo not only reduced cardiac SUMO2/Stat1 levels and pathological hypertrophy but also alleviated macrophage infiltration and fibrosis induced by pressure overload. In conclusion, we describe a novel cardioprotective mechanism involving the ubiquitin ligase HectD3, which exerts anti-hypertrophic and anti-inflammatory effects via dual regulation of SUMO2 and Stat1.
HostingRepository	PRIDE
AnnounceDate	2021-09-09
AnnouncementXML	Submission_2021-09-09_07:15:34.069.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Tholey
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-08-11 05:04:35	ID requested
⏵ 1	2021-09-09 07:15:34	announced

Rangrez AY, Borlepawar A, Schmiedel N, Deshpande A, Remes A, Kumari M, Bernt A, Christen L, Helbig A, Jungmann A, Sossalla S, Tholey A, M, ü, ller OJ, Frank D, Frey N, The E3 ubiquitin ligase HectD3 attenuates cardiac hypertrophy and inflammation in mice. Commun Biol, 3(1):562(2020) [pubmed]

submitter keyword: Cardiac models, Proteomics, Ubiquitin ligase

Andreas Tholey
contact affiliation	AG Proteomics & Bioanalytics Institut für Experimentelle Medizin Christian-Albrechts-Universität zu Kiel 24105 Kiel, Germany
contact email	a.tholey@iem.uni-kiel.de
lab head
Andreas Tholey
contact affiliation	Systematic Proteome Research & Bioanalytics, University of Kiel
contact email	a.tholey@iem.uni-kiel.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020843
     1. Label: PRIDE project
     2. Name: The E3 ubiquitin ligase HectD3 is a novel regulator of cardiac hypertrophy and inflammation