Explore the vast range of titles available.

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. The reversible and irreversible protein posttranslational modifications, such as acetylation, methylation, phosphorylation, ubiquitination, glycosylation, SUMOylation, and redox modifications, are essential regulators in organisms and cells. This work systematically summarizes the features, regulatory mechanisms, substrates, functions, and related treatments of protein modifications and will deepen the understanding of protein modifications in health and diseases.

Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential “writers” and “erasers” responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.

Posttranslational modifications (PTMs) of proteins greatly expand proteome diversity, increase functionality, and allow for rapid responses, all at relatively low costs for the cell. PTMs play key roles in plants through their impact on signaling, gene expression, protein stability and interactions, and enzyme kinetics. Following a brief discussion of the experimental and bioinformatics challenges of PTM identification, localization, and quantification (occupancy), a concise overview is provided of the major PTMs and their (potential) functional consequences in plants, with emphasis on plant metabolism. Classic examples that illustrate the regulation of plant metabolic enzymes and pathways by PTMs and their cross talk are summarized. Recent large-scale proteomics studies mapped many PTMs to a wide range of metabolic functions. Unraveling of the PTM code, i.e. a predictive understanding of the (combinatorial) consequences of PTMs, is needed to convert this growing wealth of data into an understanding of plant metabolic regulation.

Proteins are directly involved in plant phenotypic response to ever changing environmental conditions. The ability to produce multiple mature functional proteins, i.e., proteoforms, from a single gene sequence represents an efficient tool ensuring the diversification of protein biological functions underlying the diversity of plant phenotypic responses to environmental stresses. Basically, two major kinds of proteoforms can be distinguished: protein isoforms, i.e., alterations at protein sequence level arising from posttranscriptional modifications of a single pre-mRNA by alternative splicing or editing, and protein posttranslational modifications (PTMs), i.e., enzymatically catalyzed or spontaneous modifications of certain amino acid residues resulting in altered biological functions (or loss of biological functions, such as in non-functional proteins that raised as a product of spontaneous protein modification by reactive molecular species, RMS). Modulation of protein final sequences resulting in different protein isoforms as well as modulation of chemical properties of key amino acid residues by different PTMs (such as phosphorylation, N - and O -glycosylation, methylation, acylation, S -glutathionylation, ubiquitinylation, sumoylation, and modifications by RMS), thus, represents an efficient means to ensure the flexible modulation of protein biological functions in response to ever changing environmental conditions. The aim of this review is to provide a basic overview of the structural and functional diversity of proteoforms derived from a single gene in the context of plant evolutional adaptations underlying plant responses to the variability of environmental stresses, i.e., adverse cues mobilizing plant adaptive mechanisms to diminish their harmful effects.

O‐linked‐β‐N‐acetylglucosamine (O‐GlcNAcylation) is a distinctive posttranslational protein modification involving the coordinated action of O‐GlcNAc transferase and O‐GlcNAcase, primarily targeting serine or threonine residues in various proteins. This modification impacts protein functionality, influencing stability, protein–protein interactions, and localization. Its interaction with other modifications such as phosphorylation and ubiquitination is becoming increasingly evident. Dysregulation of O‐GlcNAcylation is associated with numerous human diseases, including diabetes, nervous system degeneration, and cancers. This review extensively explores the regulatory mechanisms of O‐GlcNAcylation, its effects on cellular physiology, and its role in the pathogenesis of diseases. It examines the implications of aberrant O‐GlcNAcylation in diabetes and tumorigenesis, highlighting novel insights into its potential role in cardiovascular diseases. The review also discusses the interplay of O‐GlcNAcylation with other protein modifications and its impact on cell growth and metabolism. By synthesizing current research, this review elucidates the multifaceted roles of O‐GlcNAcylation, providing a comprehensive reference for future studies. It underscores the potential of targeting the O‐GlcNAcylation cycle in developing novel therapeutic strategies for various pathologies. The levels of O‐GlcNAcylation must be maintained within a certain “optimal zone” to preserve normal cellular function. Under stimuli or abnormal nutrient intake, the levels of O‐GlcNAcylation in cells might be disrupted due to the mutual regulation between OGT and OGA, leading to the loss of O‐GlcNAc homeostasis, which is a significant factor in the pathogenesis of various human diseases.

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

New types of modifications of histones keep emerging. Recently, histone H4K8 2-hydroxyisobutyrylation (H4K8hib) was identified as an evolutionarily conserved modification. However, how this modification is regulated within a cell is still elusive, and the enzymes adding and removing 2-hydroxyisobutyrylation have not been found. Here, we report that the amount of H4K8hib fluctuates in response to the availability of carbon source in Saccharomyces cerevisiae and that low-glucose conditions lead to diminished modification. The removal of the 2-hydroxyisobutyryl group from H4K8 is mediated by the histone lysine deacetylase Rpd3p and Hos3p in vivo. In addition, eliminating modifications at this site by alanine substitution alters transcription in carbon transport/metabolism genes and results in a reduced chronological life span (CLS). Furthermore, consistent with the glucose-responsive H4K8hib regulation, proteomic analysis revealed that a large set of proteins involved in glycolysis/gluconeogenesis are modified by lysine 2-hydroxyisobutyrylation. Cumulatively, these results established a functional and regulatory network among Khib, glucose metabolism, and CLS.

Main conclusion Carbonylation-ROS-dependent posttranslational modification of proteins-may be regarded as one of the important events in the process of ageing or senescence in plants. Ageing is the progressive process starting from seed development (plants) and birth (animals). The life-span of living organisms depends on many factors and stresses, which influence reactive oxygen species (ROS) level. The imbalance of their production and scavenging causes pathophysiological conditions that accelerate ageing. ROS modify nucleic acids, lipids, sugars and proteins. The level of carbonylated proteins can serve as an indicator of an oxidative cellular status. Several pathways of protein carbonylation, e.g. the conjugation with reactive carbonyl species, and/or a direct metal-catalysed oxidative attack on amino acids residues are known. Dysfunctional carbonylated proteins are more prone to degradation or form aggregates when the proteolytic machinery is inhibited, as observed in ageing. Protein carbonylation may contribute to formation of organelle-specific signal and to the control of protein quality. Carbonylated proteins are formed during the whole plant life; nevertheless, accelerated ageing stimulates the accumulation of carbonyl derivatives. In the medicine-related literature, concerned ageing and ROS-mediated protein modifications, this topic is extensively analysed, in comparison to the plant science. In plant science, ageing and senescence are considered to describe slightly different processes (physiological events). However, senescence (Latin: senēscere ) means “to grow old”. This review describes the correlation of protein carbonylation level to ageing or/and senescence in plants. Comparing data from the area of plant and animal research, it is assumed that some basic mechanism of time-dependent alterations in the cellular biochemical processes are common and the protein carbonylation is one of the important causes of ageing.

Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease.

The conjugation of small ubiquitin-like modifiers (SUMO) to target proteins, known as SUMOylation, plays a crucial role in regulating protein homeostasis, activity, interaction with other proteins, and subcellular localization. Loss of SUMOylation in nongrowing oocytes by conditional deletion of the E2 SUMO conjugating enzyme, Ube2i, at the primordial follicle stage leads to female sterility due to complex changes in oocyte development, including altered folliculogenesis, defective meiotic progression, and premature loss of the ovarian reserve. In this study, proteomics was used to compare control and Ube2i conditional knockout ovaries during the first wave of folliculogenesis to identify key differences that may drive the premature follicle loss phenotype. Label-free mass spectrometry results showed that 238 proteins were significantly altered more than 2-fold (p<0.05). Proteins upregulated in the Ube2i conditional knockout ovaries included those involved in mRNA splicing and WNT signaling, while those downregulated were related to metabolism, mitochondria, and the maternal effect proteins NLRP2 and NLRP9B. The majority of differentially expressed proteins showed no change by transcriptome analysis, indicating protein level regulation and revealing potential SUMOylation targets with necessary roles in oocyte and follicle development. Summary Sentence Loss of SUMOylation in ovaries disrupts networks related to splicing, metabolism, and WNT signaling. Graphical Abstract