Department of Cardiology, Pulmonology and Nephrology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
Int J Mol Sci. 2021 Jun 4;22(11):6065. doi: 10.3390/ijms22116065.
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.
尽管医学取得了进步，但心脏疾病仍然是一个日益严重的健康问题，与高死亡率有关。适应性心脏重构，如心脏肥大和纤维化，是心力衰竭的一个危险因素；因此，确定新的治疗靶点至关重要。据报道，衰竭的心脏与泛素化过度和泛素蛋白酶体系统的损伤有关，这表明泛素化在心脏疾病的发展中很重要。泛素化是一种翻译后修饰，在蛋白质功能和降解中起着关键作用。1995 年，同源物到 E6AP C 端（HECT）型 E3 连接酶被发现。E3 连接酶是泛素化的关键酶，分为三类：真正有趣的新基因（RING）、HECT 和 RING 之间的 RING（RBRs）。此外，人类已鉴定出 28 种 HECT 型 E3 连接酶。它在进化中高度保守，其特征是将泛素直接附着到底物上。据报道，HECT 型 E3 连接酶参与了广泛的人类疾病和健康。在过去的十年中，已经揭示了 HECT 型 E3 连接酶在心脏疾病发展中的作用。只有少数几篇综述文章总结了心脏疾病领域 HECT 型 E3 连接酶的最新进展。本研究侧重于心脏重构，并描述了 HECT 型 E3 连接酶在心脏疾病发展中的作用。此外，本研究表明，目前的知识可以被利用来开发新的临床治疗方法。
