| First Author | Thottakara T | Year | 2015 |
| Journal | J Mol Cell Cardiol | Volume | 87 |
| Pages | 214-24 | PubMed ID | 26343497 |
| Mgi Jnum | J:251576 | Mgi Id | MGI:6102779 |
| Doi | 10.1016/j.yjmcc.2015.08.020 | Citation | Thottakara T, et al. (2015) The E3 ubiquitin ligase Asb2beta is downregulated in a mouse model of hypertrophic cardiomyopathy and targets desmin for proteasomal degradation. J Mol Cell Cardiol 87:214-24 |
| abstractText | BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an autosomal-dominant disease with mutations in genes encoding sarcomeric proteins. Previous findings suggest deregulation of the ubiquitin proteasome system (UPS) in HCM in humans and in a mouse model of HCM (Mybpc3-targeted knock-in (KI) mice). In this study we investigated transcript levels of several muscle-specific E3 ubiquitin ligases in KI mice and aimed at identifying novel protein targets. METHODS AND RESULTS: Out of 9 muscle-specific E3 ligases, Asb2beta was found with the lowest mRNA level in KI compared to wild-type (WT) mice. After adenoviral-mediated Asb2beta transduction of WT neonatal mouse cardiomyocytes with either a WT or inactive Asb2beta mutant, desmin was identified as a new target of Asb2beta by mass spectrometry, co-immunoprecipitation and immunoblotting. Immunofluorescence analysis revealed a co-localization of desmin with Asb2beta at the Z-disk of the sarcomere. Knock-down of Asb2beta in cardiomyocytes resulted in higher desmin protein levels. Furthermore, desmin levels were higher in ventricular samples of HCM mice and patients than controls. CONCLUSIONS: This study identifies desmin as a new Asb2beta target for proteasomal degradation in cardiomyocytes and suggests that accumulation of desmin could contribute to UPS impairment in HCM mice and patients. |
