Emergence of Members of TRAF and DUB of Ubiquitin Proteasome System in the Regulation of Hypertrophic Cardiomyopathy

Abstract

The ubiquitin proteasome system (UPS) plays an imperative role in many critical cellular processes, frequently by mediating the selective degradation of misfolded and damaged proteins and also by playing a non-degradative role especially important as in many signaling pathways. Over the last three decades, accumulated evidence indicated that UPS proteins are primal modulators of cell cycle progression, DNA replication, and repair, transcription, immune responses, and apoptosis. Comparatively, latest studies have demonstrated a substantial complexity by the UPS regulation in the heart. In addition, various UPS proteins especially ubiquitin ligases and proteasome have been identified to play a significant role in the cardiac development and dynamic physiology of cardiac pathologies such as ischemia/reperfusion injury, hypertrophy, and heart failure. However, our understanding of the contribution of UPS dysfunction in the plausible development of cardiac pathophysiology and the complete list of UPS proteins regulating these afflictions is still in infancy. The recent emergence of the roles of TNF receptor-associated factor (TRAFs) and deubiquitinating enzymes (DUBs) superfamily in hypertrophic cardiomyopathy has enhanced our knowledge. In this review, we have mainly compiled the TRAF superfamily of E3 ligases and few DUBs proteins with other well-documented E3 ligases such as MDM2, MuRF-1, Atrogin-I, and TRIM 32 that are specific to myocardial hypertrophy. In this review, we also aim to highlight their expression profile following physiological and pathological stimulation leading to the onset of hypertrophic phenotype in the heart that can serve as biomarkers and the opportunity for the development of novel therapies.

TRIMming down to TRIM37: Relevance to Inflammation, Cardiovascular Disorders, and Cancer in MULIBREY Nanism

“…It interacts with itself and can form hetero- and homo-oligomeric structures. The MATH domain is shared with other ubiquitin ligases, called TRAFs, and is involved in facilitating protein–protein interactions [11]. The MATH domain is thus also known as Tumor-necrosis-factor (TNF) receptor-associated factor (TRAF)-C domain.…”

Tripartite motif 10 regulates cardiac hypertrophy by targeting the PTEN/AKT pathway

“…8 In addition, mounting evidence has demonstrated that many TRIMs, including TRIM8/21/24/32/45/67/72, play important roles in cardiac function and disease, for example by regulating cardiomyocyte differentiation and apoptosis, cardiac atrophy, ischemia-reperfusion injury, and dilated and hypertrophic cardiomyopathies. [8][9][10] TRIM10, another member of the TRIM family, is essential for the differentiation and survival of terminal erythroid cells. 11 However, functional roles and molecular mechanisms of TRIM10 during cardiac hypertrophy remain to be elucidated.…”

The functional insight into the genetics of cardiovascular disease: results from the post-GWAS study

“…In short, the findings suggest that UPS contributes to structural remodeling of the myocardium, ischemia-reperfusion injury and myocardial cell loss, important components of progressive heart failure. There is evidence for the non-degradative role as well, as the ubiquitination was shown to affect the important The functional insight into the genetics of cardiovascular disease: results from the post-GWAS study regulators of signaling pathways including those for the cell growth and apoptosis, DNA damage response, the innate immune response, endocytosis, and protein activity (reviewed partly in (Gupta et al, 2018)). Given that proteostasis is a dynamic multiple-step process involving complex molecular machinery, the deregulation at any stage could therefore be implicated in a wide variety of outcomes.…”