Introduction

Protein post-translational modifications (PTMs), including acylation, ubiquitination, and other modifications, are the key regulators of gene expression and cellular homeostasis. Dysregulation of these modification dynamics is closely linked to the pathogenesis of diverse human diseases, from cancer to inflammatory disorders. This Research Topic aims to assemble cutting-edge studies that decode the molecular mechanisms of PTMs and their implications in clinical potentials, providing new insights for disease diagnosis, prognosis, and targeted therapy. Below, we synthesize the core findings of four contributing articles, contextualize their scientific significance, and highlight the collective advances of this Research Topic.

Crotonylation regulation of cancer chemoresistance

A central focus of this Research Topic is the role of epigenetic modifications in cancer progression and therapeutic resistance. Sun et al. uncovered a novel mechanism by which p53 deficiency induces cisplatin resistance in colorectal cancer. Their study identified that p53 deficiency downregulates the decrotonylase SIRT7, leading to enhanced crotonylation of ribonucleotide reductase subunit M2 (RRM2) at the K283 site. This modification promotes RRM2 expression and activity, upregulates cisplatin resistance-related genes (ATP7A, ATP7B, MUC16) and inhibits apoptotic signaling (cleaved-PARP1/cleaved-caspase3), ultimately facilitating cancer cell survival under chemotherapy. This contributing work not only reveals a new epigenetic regulatory pathway in cancer but also identifies RRM2 crotonylation as a potential therapeutic target to overcome chemoresistance, addressing an unmet clinical need in colorectal cancer treatment.

Epigenetic biomarkers for sepsis diagnosis and prognosis

Another critical theme of this Research Topic is the identification of epigenetic-related biomarkers for disease diagnosis. Cheng et al. focused on sepsis, a life-threatening inflammatory disorder characterized by immune dysregulation. They utilized integrated bioinformatics approaches including transcriptomic analysis and machine learning to screen histone acetylation-related biomarkers. Several key biomarkers, such as BLOC1S1, NDUFA1, and SFT2D1, were identified as a predictive nomogram and showing strong diagnostic potential. Furthermore, single-cell RNA sequencing linked these biomarkers to macrophage activity, shedding new light on the immunological mechanisms of sepsis. This contributing work provides a panel of epigenetic biomarkers for early sepsis diagnosis and risk stratification, which could significantly improve patient outcomes.

Ubiquitination in the host-pathogen interplay

The contributing work by Feng et al. expands our understanding of the host-pathogen interplay during Mycobacterium tuberculosis (Mtb) infection. Through a systematic analysis of the protein ubiquitinome in human macrophages, the authors identified over 1,600 proteins with altered ubiquitination levels upon Mtb infection. Notably, the study revealed that these ubiquitination changes extensively affect not only immune-related pathways like autophagy and NF-κB signaling, but also fundamental cellular processes such as ribosome biogenesis, spliceosome, and mRNA surveillance. This comprehensive resource sheds light on how microbes manipulate host post-translational modifications to survive, providing critical insights into the molecular basis of infectious diseases and potential therapeutic targets.

Lactylation in regulating metabolism and disease

Zhao et al. provided a comprehensive review of lysine lactylation, a relatively newly identified epigenetic modification. They summarized current knowledge regarding its discovery history, regulatory enzymes, and detection strategies. Notably, the review clarifies that lactylation encompasses three isomers—KL-la, KD-la, and Kce—and emphasizes that its regulatory mechanisms exhibit strong evolutionary conservation across both prokaryotes and eukaryotes. As a critical ‘metabolic-epigenetic bridge’, lactylation links cellular metabolic status to gene regulation in diverse diseases, providing a theoretical foundation for targeting metabolic-epigenetic crosstalk in future treatments.

Conclusion

Collectively, the studies in this Research Topic underscore a central theme, i.e., the intricate interplay between protein post-translational modifications and human disease regulations. A key future direction will be to move beyond individual modifications and explore the complex crosstalk between these diverse PTMs. Understanding their collective impact on disease pathogenesis will be essential for developing the next-generation of combination therapies that target multiple epigenetic and metabolic nodes. We thank all contributing authors for their valuable work, which has made this Research Topic a comprehensive resource for researchers in biosciences and clinical medicine. We also appreciate the efforts of reviewers in shaping this collection.

StatementsAuthor contributions

SC: Writing – review and editing, Writing – original draft. TL: Writing – review and editing. JX: Writing – review and editing. GZ: Writing – review and editing. LZ: Writing – review and editing. WZ: Writing – review and editing, Supervision, Validation.

Funding

The author(s) declared that financial support was received for this work and/or its publication. The Lab was supported in part by National Key Research and Development Program of China (2024YFB4105700), the National Natural Science Foundation of China (32471494 and 32570137).

Acknowledgments

We thank the Editorial Office of Frontiers in Molecular Biosciences for their support in organizing this Research Topic.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Keywords

crotonylation, disease biomarkers, histone acetylation, post-translational modifications, therapeutic targets, ubiquitination

Citation

Cheng S, Liu T, Xing J, Zhang G, Zhang L and Zhao W (2026) Editorial: Unraveling enzyme-substrate dynamics in protein acylation and disease implications. Front. Mol. Biosci. 13:1842734. doi: 10.3389/fmolb.2026.1842734

Received

30 March 2026

Revised

31 March 2026

Accepted

06 April 2026

Published

14 April 2026

Volume

13 - 2026

Edited and reviewed by

Graça Soveral, University of Lisbon, Portugal

Updates

Copyright

© 2026 Cheng, Liu, Xing, Zhang, Zhang and Zhao.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Wei Zhao, wei.zhao1@siat.ac.cn; Lin Zhang, zhanglin@suat-sz.edu.cn

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.