Abstract
Despite advances in medicine, cardiac disease remains an increasing health problem associated with a high mortality rate. Maladaptive cardiac remodeling, such as cardiac hypertrophy and fibrosis, is a risk factor for heart failure; therefore, it is critical to identify new therapeutic targets. Failing heart is reported to be associated with hyper-ubiquitylation and impairment of the ubiquitin–proteasome system, indicating an importance of ubiquitylation in the development of cardiac disease. Ubiquitylation is a post-translational modification that plays a pivotal role in protein function and degradation. In 1995, homologous to E6AP C-terminus (HECT) type E3 ligases were discovered. E3 ligases are key enzymes in ubiquitylation and are classified into three families: really interesting new genes (RING), HECT, and RING-between-RINGs (RBRs). Moreover, 28 HECT-type E3 ligases have been identified in human beings. It is well conserved in evolution and is characterized by the direct attachment of ubiquitin to substrates. HECT-type E3 ligase is reported to be involved in a wide range of human diseases and health. The role of HECT-type E3 ligases in the development of cardiac diseases has been uncovered in the last decade. There are only a few review articles summarizing recent advancements regarding HECT-type E3 ligase in the field of cardiac disease. This study focused on cardiac remodeling and described the role of HECT-type E3 ligases in the development of cardiac disease. Moreover, this study revealed that the current knowledge could be exploited for the development of new clinical therapies.
Highlights
SMURF1 interacted with SMAD6 and that this SMURF1/SMAD6 complex was involved in BMP2 antagonization of TGF-β1 mediated protein kinase C-δ and SMAD3 signaling in cardiomyocytes [89]
This study shows the current understanding of the role of homologous to E6associated protein (E6AP) C-terminus (HECT)-type E3 ligases in the development of cardiac disease
Regulation of HECT-type E3 ligases plays an important role in determining cell fate, and HECT-type E3 ligase function is implicated in cardiac disease
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. In the 2000s, many studies focused on the cardiac ubiquitin E3 ligases to clarify the role of ubiquitylation in the development of cardiac diseases, such as the carboxyl terminus of Hsp interacting protein (CHIP), atrogen-1, muscle ring finger (MuRF) family, mouse double mutant. HECT-type E3 ligase is reported to be involved in a wide range of human diseases and health including neurodegenerative diseases, neurological syndromes, and cancers [20,21,22]. It is considered as an intriguing target in drug discovery in the context of cancer biology [23]. This study revealed that the current knowledge can be exploited for the development of new clinical therapies
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