The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Protein lysine β-hydroxybutyrylation (Kbhb) is a newly discovered post-translational modification associated with a wide range of biological processes. Identifying Kbhb sites is critical for a better understanding of its mechanism of action. However, biochemical experimental methods for probing Kbhb sites are costly and have a long cycle. Therefore, a feature embedding learning method based on the Transformer encoder was proposed to predict Kbhb sites. In this method, amino acid residues were mapped into numerical vectors according to their amino acid class and position in a learnable feature embedding method. Then the Transformer encoder was used to extract discriminating features, and the bidirectional long short-term memory network (BiLSTM) was used to capture the correlation between different features. In this paper, a benchmark dataset was constructed, and a Kbhb site predictor, AutoTF-Kbhb, was implemented based on the proposed method. Experimental results showed that the proposed feature embedding learning method could extract effective features. AutoTF-Kbhb achieved an area under curve (AUC) of 0.87 and a Matthews correlation coefficient (MCC) of 0.37 on the independent test set, significantly outperforming other methods in comparison. Therefore, AutoTF-Kbhb can be used as an auxiliary means to identify Kbhb sites.
Protein Processing, Post-Translational ; Lysine/chemistry* ; Proteins/chemistry* ; Machine Learning ; Algorithms

Deactivation of the mitochondrial pyruvate dehydrogenase complex (PDC) is important for the metabolic switching of cancer cell from oxidative phosphorylation to aerobic glycolysis. Studies examining PDC activity regulation have mainly focused on the phosphorylation of pyruvate dehydrogenase (E1), leaving other post-translational modifications largely unexplored. Here, we demonstrate that the acetylation of Lys 488 of pyruvate dehydrogenase complex component X (PDHX) commonly occurs in hepatocellular carcinoma, disrupting PDC assembly and contributing to lactate-driven epigenetic control of gene expression. PDHX, an E3-binding protein in the PDC, is acetylated by the p300 at Lys 488, impeding the interaction between PDHX and dihydrolipoyl transacetylase (E2), thereby disrupting PDC assembly to inhibit its activation. PDC disruption results in the conversion of most glucose to lactate, contributing to the aerobic glycolysis and H3K56 lactylation-mediated gene expression, facilitating tumor progression. These findings highlight a previously unrecognized role of PDHX acetylation in regulating PDC assembly and activity, linking PDHX Lys 488 acetylation and histone lactylation during hepatocellular carcinoma progression and providing a potential biomarker and therapeutic target for further development.
Humans ; Acetylation ; Carcinoma, Hepatocellular/genetics* ; Liver Neoplasms/genetics* ; Pyruvate Dehydrogenase Complex/genetics* ; Gene Expression Regulation, Neoplastic ; Animals ; Mice ; Cell Line, Tumor ; Protein Processing, Post-Translational ; Histones/metabolism* ; Disease Progression

Ribosomally synthesized and post-translationally modified peptides (RiPPs) constitute a vast and diverse family of bioactive peptides. These peptides, synthesized by ribosomes and subsequently modified by various tailoring enzymes, possess a wide chemical space. Among these modifications, radical S-adenosylmethionine (rSAM) enzymes employ unique radical chemistry to introduce a variety of novel peptide structures, which are crucial for their activity. This review examines the major types of modifications in RiPPs catalyzed by rSAM enzymes, incorporating recent advancements in protein structure analysis techniques and computational methods. Additionally, it elucidates the diverse catalytic mechanisms and substrate selectivity of these enzymes through an analysis of the latest crystal structures.
Protein Processing, Post-Translational ; S-Adenosylmethionine/chemistry* ; Ribosomes/metabolism* ; Peptides/metabolism* ; Biological Products/metabolism* ; Humans

Abiotic stresses substantially affect the growth and development of plants. Plants have evolved multiple strategies to cope with the environmental stresses, among which transcription factors play an important role in regulating the tolerance to abiotic stresses. Basic leucine zipper transcription factors (bZIP) are one of the largest gene families. The stability and activity of bZIP transcription factors could be regulated by different post-translational modifications (PTMs) in response to various intracellular or extracellular stresses. This paper introduces the structural feature and classification of bZIP transcription factors, followed by summarizing the PTMs of bZIP transcription factors, such as phosphorylation, ubiquitination and small ubiquitin-like modifier (SUMO) modification, in response to abiotic stresses. In addition, future perspectives were prospected, which may facilitate cultivating excellent stress-resistant crop varieties by regulating the PTMs of bZIP transcription factors.
Basic-Leucine Zipper Transcription Factors/genetics* ; Protein Processing, Post-Translational ; Phosphorylation ; Transcription Factors/genetics* ; Stress, Physiological/genetics*

The N-end rule pathway is a protein degradation pathway mediated by the ubiquitin-proteasome system, which specifically targets and degrades target proteins by recognizing specific residues at the N-terminus of the proteins. The residues which play a crucial role in the N-end rule pathway are called degrons, also known as N-degrons, as they are usually unstable at the N-terminal end of the protein. Currently, several N-end rule pathways have been identified in the eukaryotes, including the Arg/N-end rule, Ac/N-end rule, and Pro/N-end rule pathways, as well as the recently discovered Gly/N-end rule pathway. The Ac/N-end rule pathway targets proteins containing N-terminal acetylation (Nt-acetylation) residues. The Arg/N-end rule pathway, on the other hand, targets certain unacetylated residues and involves N-terminal arginylation. For proteins with N-terminal proline (Pro) and glycine (Gly) residues, they are neither modified by acetylation nor recognized through the Arg/N-end rule pathway. Therefore, these proteins are primarily recognized and degraded through the Pro/N-end rule pathway and the Gly/N-end rule pathway. The regulation of specific proteins through N-end rule pathway-mediated degradation plays an important role in numerous physiological and pathological processes, such as cardiovascular development, neurogenesis, meiosis, spermatogenesis, HPV infection, and cell apoptosis. In this review, we summarize the role and mechanisms of several known N-end rule pathways and discuss their relationship with certain diseases. As an independent protein degradation system, the N-end rule pathways still hold countless biological secrets waiting for exploring. The comprehensive understanding of these pathways could potentially uncover novel therapeutic targets for various diseases.
Humans ; Proteolysis ; Animals ; Proteasome Endopeptidase Complex/physiology* ; Acetylation ; Proteins/metabolism* ; Protein Processing, Post-Translational ; Ubiquitin/metabolism*

The ovary is the reproductive organ of female mammals, which is responsible for producing mature eggs and secreting sex hormones. The regulation of ovarian function involves the ordered activation and repression of genes related to cell growth and differentiation. In recent years, it has been found that histone posttranslational modification can affect DNA replication, damage repair and gene transcriptional activity. Some regulatory enzymes mediating histone modification are co-activators or co-inhibitors associated with transcription factors, which play important roles in the regulation of ovarian function and the development of ovary-related diseases. Therefore, this review outlines the dynamic patterns of common histone modifications (mainly acetylation and methylation) during the reproductive cycle and their regulation of gene expression for important molecular events, focusing on the mechanisms of follicle development and sex hormone secretion and function. For example, the specific dynamics of histone acetylation are important for the arrest and resumption of meiosis in oocytes, while histone (especially H3K4) methylation affects the maturation of oocytes by regulating their chromatin transcriptional activity and meiotic progression. Besides, histone acetylation or methylation can also promote the synthesis and secretion of steroid hormones before ovulation. Finally, the abnormal histone posttranslational modifications in the development of two common ovarian diseases (premature ovarian insufficiency and polycystic ovary syndrome) are briefly described. It will provide a reference basis for understanding the complex regulation mechanism of ovarian function and further exploring the potential therapeutic targets of related diseases.
Female ; Animals ; Histone Code ; Histones ; Protein Processing, Post-Translational ; Ovary ; Oocytes ; Mammals

Epigenetics refers to heritable changes in gene expression and function without alterations in gene sequences,including DNA methylation,histone modification,and non-coding RNAs.Endometriosis is a benign gynecological disease that affects the fertility and health of reproductive-age women,the etiology of which remains unclear.The recent studies have demonstrated that epigenetics plays a key role in the occurrence and development of endometriosis.This article reviews the research progress in the regulatory mechanism and application of epigenetics in endometriosis.
Female ; Humans ; Endometriosis/genetics* ; Epigenesis, Genetic ; DNA Methylation ; Protein Processing, Post-Translational

Histone acetylation is one of the epigenetic modifications. Histone acetylation, which is catalyzed by histone acetyltransferases and negatively regulated by histone deacetylases, plays an important role in a variety of cellular physiological and pathophysiological processes. Recent studies have shown that histone deacetylases are involved in a variety of pathophysiological responses to acute kidney injury, such as apoptosis, dedifferentiation, proliferation and regeneration. This article reviews the role and underlying mechanism of histone deacetylases in acute kidney injury induced by ischemia reperfusion, nephrotoxicants, sepsis and rhabdomyolysis.
Acetylation ; Acute Kidney Injury ; Histone Acetyltransferases/metabolism* ; Histone Deacetylases/metabolism* ; Humans ; Protein Processing, Post-Translational

With the widespread application of genomics and transcriptomics in the genetics and cell biology of different species, synonymous codon usage bias has been gradually accepted and used to study the deep connection between biological evolution and biological phenotypes. It is an important part of the life activities that mRNA is expressed into proteins with normal biological activities. The synonymous codon usage patterns, which were named as 'the second genetic codon', can express genetic information carried by themselves at the levels of transcriptional regulations, translational regulations and metabolic activities through molecular mechanisms such as fine-tune translation selection. Some studies have shown that the length of mRNA half-life has significant impacts on mRNA activity and the process of transcription and translation. This review summarized the roles of synonymous codon usage patterns in transcription, translational regulation and post-translational modification, with the aim to better understand how organisms skillfully utilize the genetic effects caused by codon usage patterns to accurately synthesize different types of proteins, so as to ensure the growth or differentiation of the specific gene expression procedures to carry out smoothly and maintain the normal life cycle.
Codon/genetics* ; Codon Usage ; Half-Life ; Protein Processing, Post-Translational ; RNA, Messenger/genetics*