Posttranslational modifications in diabetes: Mechanisms and functions

Hu, Ang; Zou, Haohong; Chen, Bin; Zhong, Jianing

doi:10.1007/s11154-022-09740-x

Cited by 6 publications

(6 citation statements)

References 189 publications

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“… 1019 Furthermore, SUMOylation can prevent stress‐induced β‐cell apoptosis by upregulating the levels of antioxidant genes, including Ho‐1 , Cat , and Nqo‐1 . 1020 ERK5 is one of the major targets of SUMOylation in diabetic hearts. ERK5 SUMOylation enhances the inhibition of ROS‐mediated ERK5 transcription, which leads to the deterioration of left ventricular function after myocardial infarction in diabetic.…”

Section: Sumoylationmentioning

confidence: 99%

“…The E3 SUMO ligase PIASy can inhibit insulin secretion by reducing the interaction between ICA512 and STAT5 through SUMOylation of ICA512 1019 . Furthermore, SUMOylation can prevent stress‐induced β‐cell apoptosis by upregulating the levels of antioxidant genes, including Ho‐1 , Cat , and Nqo‐1 1020 . ERK5 is one of the major targets of SUMOylation in diabetic hearts.…”

Section: Sumoylationmentioning

confidence: 99%

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Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on the backbones or amino acid side chains of proteins and expand the diversity of proteins, which provides the basis for the emergence of organismal complexity. To date, more than 650 types of protein modifications, such as the most well‐known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short‐chain and long‐chain acylation modifications, redox modifications, and irreversible modifications, have been described, and the inventory is still increasing. By changing the protein conformation, localization, activity, stability, charges, and interactions with other biomolecules, PTMs ultimately alter the phenotypes and biological processes of cells. The homeostasis of protein modifications is important to human health. Abnormal PTMs may cause changes in protein properties and loss of protein functions, which are closely related to the occurrence and development of various diseases. In this review, we systematically introduce the characteristics, regulatory mechanisms, and functions of various PTMs in health and diseases. In addition, the therapeutic prospects in various diseases by targeting PTMs and associated regulatory enzymes are also summarized. This work will deepen the understanding of protein modifications in health and diseases and promote the discovery of diagnostic and prognostic markers and drug targets for diseases.

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Section: Sumoylationmentioning

confidence: 99%

Section: Sumoylationmentioning

confidence: 99%

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Zhong

Xiao

Xie

et al. 2023

MedComm

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“…Furthermore, the oxidative stress resulting from lipid buildup can directly lead to PTMs of proteins [37]. Both oxidation and carbonylation are closely linked to oxidative stress and occur through non-enzymatic processes [38]. Among these, carbonylation, a PTM catalyzed by metals, affects lysine, proline, arginine, and threonine residues within proteins.…”

Section: Fa-induced Post-translational Modifications (Ptms)mentioning

confidence: 99%

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia

Chae,

Kim,

Park

2023

Antioxidants

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Oxidative stress, a hallmark pathophysiological feature in diabetic kidney disease (DKD), arises from the intricate interplay between pro-oxidants and anti-oxidants. While hyperglycemia has been well established as a key contributor, lipotoxicity emerges as a significant instigator of oxidative stress. Lipotoxicity encompasses the accumulation of lipid intermediates, culminating in cellular dysfunction and cell death. However, the mechanisms underlying lipotoxic kidney injury in DKD still require further investigation. The key role of cell metabolism in the maintenance of cell viability and integrity in the kidney is of paramount importance to maintain proper renal function. Recently, dysfunction in energy metabolism, resulting from an imbalance in oxygen levels in the diabetic condition, may be the primary pathophysiologic pathway driving DKD. Therefore, we aim to shed light on the pivotal role of oxidative stress related to lipotoxicity and renal hypoxia in the initiation and progression of DKD. Multifaceted mechanisms underlying lipotoxicity, including oxidative stress with mitochondrial dysfunction, endoplasmic reticulum stress activated by the unfolded protein response pathway, pro-inflammation, and impaired autophagy, are delineated here. Also, we explore potential therapeutic interventions for DKD, targeting lipotoxicity- and hypoxia-induced oxidative stress. These interventions focus on ameliorating the molecular pathways of lipid accumulation within the kidney and enhancing renal metabolism in the face of lipid overload or ameliorating subsequent oxidative stress. This review highlights the significance of lipotoxicity, renal hypoxia-induced oxidative stress, and its potential for therapeutic intervention in DKD.

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“…Later, lysine acetylation in histones was discovered by Vincent Allfrey in 1964 . During the past decade, PTM studies have encountered a new era with the development of advanced proteomics techniques that have identified more than 600 distinct types of PTMs in thousands of proteins covering almost all the biological processes in bacteria, archaea, and eukarya. − PTMs can change charges of protein side chains such as phosphorylation and acetylation to affect substrate binding or interactions with other biomolecules. − PTMs can also add specific tags to proteins for triggering corresponding biological processes such as ubiquitination and glycosylation. − More importantly, PTMs have been found to be closely associated with a variety of human diseases including cancers, cardiovascular diseases, diabetes, neurodegenerative diseases, and even coronavirus diseases in the recent COVID-19 pandemic . Thus, protein PTMs have been attracting attentions of scientists from different research fields for decades.…”

Section: Introductionmentioning

confidence: 99%

Orthogonal Translation for Site-Specific Installation of Post-translational Modifications

Gan,

Fan

2024

Chem. Rev.

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Post-translational modifications (PTMs) endow proteins with new properties to respond to environmental changes or growth needs. With the development of advanced proteomics techniques, hundreds of distinct types of PTMs have been observed in a wide range of proteins from bacteria, archaea, and eukarya. To identify the roles of these PTMs, scientists have applied various approaches. However, high dynamics, low stoichiometry, and crosstalk between PTMs make it almost impossible to obtain homogeneously modified proteins for characterization of the site-specific effect of individual PTM on target proteins. To solve this problem, the genetic code expansion (GCE) strategy has been introduced into the field of PTM studies. Instead of modifying proteins after translation, GCE incorporates modified amino acids into proteins during translation, thus generating site-specifically modified proteins at target positions. In this review, we summarize the development of GCE systems for orthogonal translation for site-specific installation of PTMs.

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Posttranslational modifications in diabetes: Mechanisms and functions

Cited by 6 publications

References 189 publications

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia

Orthogonal Translation for Site-Specific Installation of Post-translational Modifications

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