Dataset Information

The E3 ubiquitin ligase HectD3 is a novel regulator of cardiac hypertrophy and inflammation

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart

SUBMITTER: Andreas Tholey

LAB HEAD: Andreas Tholey

PROVIDER: PXD020843 | Pride | 2021-09-09

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	AH_111217_HEKD3_overexpression_TMT_0.pdResult	Other
	AH_111217_HEKD3_overexpression_TMT_01.mzML	Mzml
	AH_111217_HEKD3_overexpression_TMT_01_171213071450.mzML	Mzml
	AH_111217_HEKD3_overexpression_TMT_02.mzML	Mzml
	AH_111217_HEKD3_overexpression_TMT_02_171215084340.mzML	Mzml

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Publications

The E3 ubiquitin ligase HectD3 attenuates cardiac hypertrophy and inflammation in mice.

Rangrez Ashraf Yusuf AY Borlepawar Ankush A Schmiedel Nesrin N Deshpande Anushka A Remes Anca A Kumari Manju M Bernt Alexander A Christen Lynn L Helbig Andreas A Jungmann Andreas A Sossalla Samuel S Tholey Andreas A Müller Oliver J OJ Frank Derk D Frey Norbert N

Communications biology 20201009 1

Myocardial inflammation has recently been recognized as a distinct feature of cardiac hypertrophy and heart failure. HectD3, a HECT domain containing E3 ubiquitin ligase has previously been investigated in the host defense against infections as well as neuroinflammation; its cardiac function however is still unknown. Here we show that HectD3 simultaneously attenuates Calcineurin-NFAT driven cardiomyocyte hypertrophy and the pro-inflammatory actions of LPS/interferon-γ via its cardiac substrates ...[more]

PMID: 33037313

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