Research progress on post-translational modification of proteins and cardiovascular diseases

Cheng, Xueli; Wang, Kai; Zhao, Yan; Wang, Kun

doi:10.1038/s41420-023-01560-5

Cited by 7 publications

(5 citation statements)

References 118 publications

(103 reference statements)

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“…Since the 1990s, it was discovered that variants in ion channels are responsible for trafficking defects, leading to the development of HF and arrhythmias ( Figure 3A ) ( 199 ). Also, several abnormal post-translational modifications, which affect many cellular pathways, have been reported in patients with HF ( 183 ). Among these modifications, alterations in phosphorylation, glycosylation, ubiquitin, acetylation, and succinylation were reported ( 168 , 200 , 201 ).…”

Section: Ion Channel Trafficking Defect Contributes To the Developmen...mentioning

confidence: 99%

Ion channel trafficking implications in heart failure

Reisqs,

Qu,

Boutjdir

2024

Front. Cardiovasc. Med.

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Heart failure (HF) is recognized as an epidemic in the contemporary world, impacting around 1%–2% of the adult population and affecting around 6 million Americans. HF remains a major cause of mortality, morbidity, and poor quality of life. Several therapies are used to treat HF and improve the survival of patients; however, despite these substantial improvements in treating HF, the incidence of HF is increasing rapidly, posing a significant burden to human health. The total cost of care for HF is USD 69.8 billion in 2023, warranting a better understanding of the mechanisms involved in HF. Among the most serious manifestations associated with HF is arrhythmia due to the electrophysiological changes within the cardiomyocyte. Among these electrophysiological changes, disruptions in sodium and potassium currents’ function and trafficking, as well as calcium handling, all of which impact arrhythmia in HF. The mechanisms responsible for the trafficking, anchoring, organization, and recycling of ion channels at the plasma membrane seem to be significant contributors to ion channels dysfunction in HF. Variants, microtubule alterations, or disturbances of anchoring proteins lead to ion channel trafficking defects and the alteration of the cardiomyocyte's electrophysiology. Understanding the mechanisms of ion channels trafficking could provide new therapeutic approaches for the treatment of HF. This review provides an overview of the recent advances in ion channel trafficking in HF.

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Section: Ion Channel Trafficking Defect Contributes To the Developmen...mentioning

confidence: 99%

Ion channel trafficking implications in heart failure

Reisqs,

Qu,

Boutjdir

2024

Front. Cardiovasc. Med.

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“…PTMs play a central role in a wide range of biological processes, including cell signaling pathway, immune response, DNA damage response, and metabolism ( 3 , 4 ). Dysregulation of PTMs is associated with various diseases, including cancer ( 5 – 7 ), neurodegenerative disorders ( 8 , 9 ), cardiovascular diseases ( 10 ), and metabolic syndromes ( 11 , 12 ). It is critical to explore the regulatory mechanism of PTMs in order to discover the new targets for disease treatments.…”

Section: Introductionmentioning

confidence: 99%

PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

Ren,

Wang,

Liu

et al. 2024

Front. Immunol.

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Immunotherapy has been developed, which harnesses and enhances the innate powers of the immune system to fight disease, particularly cancer. PD-1 (programmed death-1) and PD-L1 (programmed death ligand-1) are key components in the regulation of the immune system, particularly in the context of cancer immunotherapy. PD-1 and PD-L1 are regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation and glycosylation. PROTACs (Proteolysis Targeting Chimeras) are a type of new drug design technology. They are specifically engineered molecules that target specific proteins within a cell for degradation. PROTACs have been designed and demonstrated their inhibitory activity against the PD-1/PD-L1 pathway, and showed their ability to degrade PD-1/PD-L1 proteins. In this review, we describe how PROTACs target PD-1 and PD-L1 proteins to improve the efficacy of immunotherapy. PROTACs could be a novel strategy to combine with radiotherapy, chemotherapy and immunotherapy for cancer patients.

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“…In eukaryotic cells, secretory and endomembrane proteins destined for many cellular organelles typically enter the endoplasmic reticulum (ER) in their unfolded states, where they undergo their initial and crucial processes to acquire their proper tertiary conformations [ 1 , 2 ]. In particular, this is where these ER-targeted proteins undergo essential post-translational modifications including glycosylation, proline isomerization, lipidation and disulfide bond formation, which are often crucial for guiding proper folding, stability and the performance of their biological functions [ 3 , 4 ]. To ensure efficiency and fidelity, cells have adapted extensive ER quality control (ERQC) mechanisms that allow only properly folded proteins to reach their functional destination [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy

Gariballa,

Mohamed,

Badawi

et al. 2024

J Biomed Sci

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The endoplasmic reticulum (ER) employs stringent quality control mechanisms to ensure the integrity of protein folding, allowing only properly folded, processed and assembled proteins to exit the ER and reach their functional destinations. Mutant proteins unable to attain their correct tertiary conformation or form complexes with their partners are retained in the ER and subsequently degraded through ER-associated protein degradation (ERAD) and associated mechanisms. ER retention contributes to a spectrum of monogenic diseases with diverse modes of inheritance and molecular mechanisms. In autosomal dominant diseases, when mutant proteins get retained in the ER, they can interact with their wild-type counterparts. This interaction may lead to the formation of mixed dimers or aberrant complexes, disrupting their normal trafficking and function in a dominant-negative manner. The combination of ER retention and dominant-negative effects has been frequently documented to cause a significant loss of functional proteins, thereby exacerbating disease severity. This review aims to examine existing literature and provide insights into the impact of dominant-negative effects exerted by mutant proteins retained in the ER in a range of autosomal dominant diseases including skeletal and connective tissue disorders, vascular disorders, neurological disorders, eye disorders and serpinopathies. Most crucially, we aim to emphasize the importance of this area of research, offering substantial potential for understanding the factors influencing phenotypic variability associated with genetic variants. Furthermore, we highlight current and prospective therapeutic approaches targeted at ameliorating the effects of mutations exhibiting dominant-negative effects. These approaches encompass experimental studies exploring treatments and their translation into clinical practice.

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Research progress on post-translational modification of proteins and cardiovascular diseases

Cited by 7 publications

References 118 publications

Ion channel trafficking implications in heart failure

Ion channel trafficking implications in heart failure

PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

The double whammy of ER-retention and dominant-negative effects in numerous autosomal dominant diseases: significance in disease mechanisms and therapy

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