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):

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart

SUBMITTER: Andreas Tholey  

LAB HEAD: Andreas Tholey

PROVIDER: PXD020843 | Pride | 2021-09-09

REPOSITORIES: Pride