Cell Chemical Biology最新文献

{"title":"Post-translational modifications in bacteria: From identification to function","authors":"Ashleigh L. Dale,&nbsp;Melanie Y. White,&nbsp;Stuart J. Cordwell","doi":"10.1016/j.chembiol.2026.08.018","DOIUrl":"10.1016/j.chembiol.2026.08.018","url":null,"abstract":"<div><div>Post-translational modifications (PTMs) provide molecular variety beyond the gene or amino acid codes. Diversity stems from a vast number of chemical species or physical changes that are regulated either enzymatically or non-enzymatically to provide transient or prolonged alterations to protein structure and function. Bacteria are wrongly considered “simple” due to their relatively small genomes; however, application of high-resolution methods in enrichment, identification, and quantitation by mass spectrometry (MS) has unleashed a plethora of site-specific PTM data unequivocally demonstrating that bacteria can undertake almost all modifications seen in eukaryotes, while also maintaining novel PTMs that occur specifically in these organisms. Despite this, our ability to exploit omics-level PTM data has not been comparable; determining site stoichiometry, understanding the roles conferred by PTMs, and characterizing the functions of identified PTM sites remain to be routinely achievable at scale. This review examines major PTMs and their importance in generating functional variations in bacterial proteins.</div></div><div>Post-translational modifications (PTMs) provide molecular variety beyond the gene or amino acid codes. Diversity stems from a vast number of chemical species or physical changes that are regulated either enzymatically or non-enzymatically to provide transient or prolonged alterations to protein structure and function. Bacteria are wrongly considered “simple” due to their relatively small genomes; however, application of high-resolution methods in enrichment, identification, and quantitation by mass spectrometry (MS) has unleashed a plethora of site-specific PTM data unequivocally demonstrating that bacteria can undertake almost all modifications seen in eukaryotes, while also maintaining novel PTMs that occur specifically in these organisms. Despite this, our ability to exploit omics-level PTM data has not been comparable; determining site stoichiometry, understanding the roles conferred by PTMs, and characterizing the functions of identified PTM sites remain to be routinely achievable at scale. This review examines major PTMs and their importance in generating functional variations in bacterial proteins.</div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (132KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1517-1543"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine methylation in immunoregulation: Mechanisms and therapeutic targeting","authors":"Song-Iee Han,&nbsp;Sachiko Toma-Fukai,&nbsp;Jun-Dal Kim,&nbsp;Koichiro Kako,&nbsp;Hiroaki Daitoku,&nbsp;Akiyoshi Fukamizu","doi":"10.1016/j.chembiol.2026.09.003","DOIUrl":"10.1016/j.chembiol.2026.09.003","url":null,"abstract":"<div><div>Post-translational modifications (PTMs) are central regulators of immune cell function, linking extracellular signals to the regulation of intracellular gene expression. Among these, protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is a key mechanism that connects epigenetic control with signal transduction. PRMTs modify both histone and non-histone substrates, thereby regulating chromatin accessibility, transcriptional programs, and immune signaling pathways. Recent studies have shown that arginine methylation modulates immune cell activation, differentiation, and effector functions, whereas its dysregulation contributes to tumor immune evasion and chronic inflammation. Notably, alterations in PRMT activity have been increasingly suggested in age-associated immune remodeling and inflammaging. In this review, we integrate current evidence showing how PRMT-mediated arginine methylation coordinates chromatin regulation, RNA metabolism, and immune signaling, and examine how these mechanisms shape immune homeostasis, tumor immunity, inflammaging, and opportunities for therapeutic intervention.</div></div><div>Post-translational modifications (PTMs) are central regulators of immune cell function, linking extracellular signals to the regulation of intracellular gene expression. Among these, protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is a key mechanism that connects epigenetic control with signal transduction. PRMTs modify both histone and non-histone substrates, thereby regulating chromatin accessibility, transcriptional programs, and immune signaling pathways. Recent studies have shown that arginine methylation modulates immune cell activation, differentiation, and effector functions, whereas its dysregulation contributes to tumor immune evasion and chronic inflammation. Notably, alterations in PRMT activity have been increasingly suggested in age-associated immune remodeling and inflammaging. In this review, we integrate current evidence showing how PRMT-mediated arginine methylation coordinates chromatin regulation, RNA metabolism, and immune signaling, and examine how these mechanisms shape immune homeostasis, tumor immunity, inflammaging, and opportunities for therapeutic intervention.</div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (198KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1422-1442"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149090235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Location, location, deUFMylation: Coordinating ribosome quality control at the ER","authors":"Alexander R. Mikesell,&nbsp;Zachary T. Campbell","doi":"10.1016/j.chembiol.2026.08.015","DOIUrl":"10.1016/j.chembiol.2026.08.015","url":null,"abstract":"<div><div>Endoplasmic-reticulum-associated ribosome quality control (ER-RQC) requires ubiquitin-fold modifier 1 (UFM1) for UFMylation of the ribosomal protein RPL26. In the August 6 issue of <em>Molecular Cell</em>, Mao et al.<span><span>¹</span></span> identify an ER-associated complex (UFSP2/ODR4) as critical for deUFMylation of RPL26 and uncover a critical physiologic role for UFSP2 in neuronal proteostasis.</div></div><div>Endoplasmic-reticulum-associated ribosome quality control (ER-RQC) requires ubiquitin-fold modifier 1 (UFM1) for UFMylation of the ribosomal protein RPL26. In the August 6 issue of <em>Molecular Cell</em>, Mao et al.<span><span>¹</span></span> identify an ER-associated complex (UFSP2/ODR4) as critical for deUFMylation of RPL26 and uncover a critical physiologic role for UFSP2 in neuronal proteostasis.</div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1353-1355"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting protein arginine methyltransferases to enhance cancer immunotherapy","authors":"Nivine Srour,&nbsp;Chunxiao Zhao,&nbsp;Stéphane Richard","doi":"10.1016/j.chembiol.2026.09.010","DOIUrl":"10.1016/j.chembiol.2026.09.010","url":null,"abstract":"<div><div>Arginine methylation is a post-translational modification found on many proteins, including RNA-binding proteins, signaling molecules, histones, and heat shock proteins, where it can alter protein-protein and protein-nucleic acid interactions. Arginine methylation regulates many cellular pathways, including RNA metabolism, signal transduction, gene expression, cellular stress responses, DNA repair, and, more recently, innate immune sensing. Here, we discuss recent advances in innate immune sensing and the emerging role of arginine methylation in suppressing tumor immune visibility. We describe current knowledge of protein arginine methyltransferase (PRMT) inhibitors and degraders and their use from preclinical models to clinical trials, alone or in combination with other therapies, to reduce tumor progression and enhance the effectiveness of cancer immunotherapy.</div></div><div>Arginine methylation is a post-translational modification found on many proteins, including RNA-binding proteins, signaling molecules, histones, and heat shock proteins, where it can alter protein-protein and protein-nucleic acid interactions. Arginine methylation regulates many cellular pathways, including RNA metabolism, signal transduction, gene expression, cellular stress responses, DNA repair, and, more recently, innate immune sensing. Here, we discuss recent advances in innate immune sensing and the emerging role of arginine methylation in suppressing tumor immune visibility. We describe current knowledge of protein arginine methyltransferase (PRMT) inhibitors and degraders and their use from preclinical models to clinical trials, alone or in combination with other therapies, to reduce tumor progression and enhance the effectiveness of cancer immunotherapy.</div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1443-1458"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voices: Emerging molecular mechanisms and open questions in post-translational modifications","authors":"Lauren V. Albrecht,&nbsp;Xiucong Bao,&nbsp;Philip A. Cole,&nbsp;Zhenyi Hu,&nbsp;Shan Li (李姗),&nbsp;Shixian Lin,&nbsp;Rebecca A. Scheck,&nbsp;Christopher Schofield,&nbsp;Amy Weeks,&nbsp;Qingfei Zheng","doi":"10.1016/j.chembiol.2026.09.017","DOIUrl":"10.1016/j.chembiol.2026.09.017","url":null,"abstract":"<div><div>Post-translational modifications expand the functional diversity of the proteome and provide dynamic control over protein activity, localization, interactions, and stability, making them fundamental regulators of cellular function. In this Voices piece accompanying a special issue on post-translational modifications in <em>Cell Chemical Biology</em>, we ask researchers from across the field: what recent advances in post-translational modification research are most exciting, what important challenges remain, and what are the next big questions for the field?</div></div><div>Post-translational modifications expand the functional diversity of the proteome and provide dynamic control over protein activity, localization, interactions, and stability, making them fundamental regulators of cellular function. In this Voices piece accompanying a special issue on post-translational modifications in <em>Cell Chemical Biology</em>, we ask researchers from across the field: what recent advances in post-translational modification research are most exciting, what important challenges remain, and what are the next big questions for the field?</div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (254KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1348-1352"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meet the authors: Cameron Douglas and Ciaran Seath","authors":"Cameron Douglas,&nbsp;Ciaran Seath","doi":"10.1016/j.chembiol.2026.09.014","DOIUrl":"10.1016/j.chembiol.2026.09.014","url":null,"abstract":"<div><div>In an interview with Samantha Nelson, a scientific editor of <em>Cell Chemical Biology</em>, the authors of the review entitled “Chemical biology tools for studying histone post-translational modifications” share their perspectives on their field and life as scientists.</div></div><div>In an interview with Samantha Nelson, a scientific editor of <em>Cell Chemical Biology</em>, the authors of the review entitled “Chemical biology tools for studying histone post-translational modifications” share their perspectives on their field and life as scientists.</div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (247KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1344-1345"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The expanding biology of post-translational modifications","authors":"George Burslem,&nbsp;The Cell Chemical Biology editorial team","doi":"10.1016/j.chembiol.2026.09.016","DOIUrl":"10.1016/j.chembiol.2026.09.016","url":null,"abstract":"","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Page 1343"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149173076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond acetylation: Evaluating the emerging biology of lysine acylation","authors":"Jordi C.J. Hintzen,&nbsp;George M. Burslem","doi":"10.1016/j.chembiol.2026.07.009","DOIUrl":"10.1016/j.chembiol.2026.07.009","url":null,"abstract":"<div><div>Lysine acylation has emerged as a rapidly expanding family of post-translational modifications that directly links cellular metabolism to protein regulation. Beyond lysine acetylation, advances in mass spectrometry and chemical biology have uncovered a diverse repertoire of acyl modifications spanning short-chain, branched, unsaturated, aromatic, and dicarboxylic groups. Together these modifications establish lysine acylation as a molecular interface through which metabolic state can shape protein function, chromatin regulation, and cell signaling. Yet fundamental questions remain regarding their biological significance, enzymatic regulation, site specificity, and whether many acylations function as bona fide regulatory signals or reflect metabolite-driven mechanisms. Here, we synthesize the current understanding of the metabolic origins, structural and biochemical properties, and their writer, reader, and eraser systems that govern lysine acylations. We further highlight emerging chemical biology approaches for detecting, manipulating, and functionally interrogating acyl marks and discuss the conceptual and technological advances needed to distinguish closely related modifications and establish their causal biological roles.</div></div><div>Lysine acylation has emerged as a rapidly expanding family of post-translational modifications that directly links cellular metabolism to protein regulation. Beyond lysine acetylation, advances in mass spectrometry and chemical biology have uncovered a diverse repertoire of acyl modifications spanning short-chain, branched, unsaturated, aromatic, and dicarboxylic groups. Together these modifications establish lysine acylation as a molecular interface through which metabolic state can shape protein function, chromatin regulation, and cell signaling. Yet fundamental questions remain regarding their biological significance, enzymatic regulation, site specificity, and whether many acylations function as bona fide regulatory signals or reflect metabolite-driven mechanisms. Here, we synthesize the current understanding of the metabolic origins, structural and biochemical properties, and their writer, reader, and eraser systems that govern lysine acylations. We further highlight emerging chemical biology approaches for detecting, manipulating, and functionally interrogating acyl marks and discuss the conceptual and technological advances needed to distinguish closely related modifications and establish their causal biological roles.</div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1544-1563"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148716659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical biology tools for studying histone post-translational modifications","authors":"Cameron J. Douglas,&nbsp;Ciaran P. Seath","doi":"10.1016/j.chembiol.2026.04.015","DOIUrl":"10.1016/j.chembiol.2026.04.015","url":null,"abstract":"<div><div>Post-translational modifications (PTMs) of histones are central regulators of chromatin organization and gene expression, providing a dynamic and reversible mechanism to encode cellular state. While advances in mass spectrometry have rapidly expanded the catalog of histone PTMs beyond classical acetylation and methylation, defining their functional roles remains a major challenge. A central bottleneck is linking specific PTMs to the enzymes that write and erase them, as well as the reader proteins that interpret them within native chromatin environments. The dysregulation of this regulatory machinery is increasingly implicated in cancer, neurodevelopmental disorders, and metabolic disease. Here, we argue that resolving PTM function requires integrating chemical precision with increasing biological complexity. We review chemical biology strategies for interrogating histone PTMs across this spectrum—from synthetic peptides to semisynthetic nucleosomes and intact chromatin—highlighting how each approach balances experimental control with physiological relevance and propose future directions for systematically mapping PTM-dependent interactions.</div></div><div>Post-translational modifications (PTMs) of histones are central regulators of chromatin organization and gene expression, providing a dynamic and reversible mechanism to encode cellular state. While advances in mass spectrometry have rapidly expanded the catalog of histone PTMs beyond classical acetylation and methylation, defining their functional roles remains a major challenge. A central bottleneck is linking specific PTMs to the enzymes that write and erase them, as well as the reader proteins that interpret them within native chromatin environments. The dysregulation of this regulatory machinery is increasingly implicated in cancer, neurodevelopmental disorders, and metabolic disease. Here, we argue that resolving PTM function requires integrating chemical precision with increasing biological complexity. We review chemical biology strategies for interrogating histone PTMs across this spectrum—from synthetic peptides to semisynthetic nucleosomes and intact chromatin—highlighting how each approach balances experimental control with physiological relevance and propose future directions for systematically mapping PTM-dependent interactions.</div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (116KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1356-1372"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13218614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148025277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the classical histone deacetylases and sirtuins using peptide technologies","authors":"Joseph M. Rogers,&nbsp;Christian A. Olsen","doi":"10.1016/j.chembiol.2026.08.009","DOIUrl":"10.1016/j.chembiol.2026.08.009","url":null,"abstract":"<div><div>Histone deacetylase (HDAC) enzymes are hydrolases that remove acyl-based modifications from the side chains of lysine residues in our proteome. Originally named after their first identified substrates, the acetylated lysine residues in histone proteins, it has now become evident that individual isozymes of the HDAC class have different protein targets, cellular localization, and ε-<em>N</em>-acyllysine substrate specificities. To help elucidate the activities of the different HDACs, researchers have developed a variety of peptide-based tools, providing mechanistic insights and substrate preferences of the HDACs. Due to their central regulatory roles, HDACs have been investigated as drug targets, resulting in several drugs approved for clinical use, including the naturally occurring peptide, romidepsin, spurring the interest in peptide-based inhibitors. In this review, we provide a concise overview of important discoveries enabled by peptide chemistry in the HDAC field and discuss the future potential of high-throughput peptide technologies for HDAC profiling and inhibitor discovery.</div></div><div>Histone deacetylase (HDAC) enzymes are hydrolases that remove acyl-based modifications from the side chains of lysine residues in our proteome. Originally named after their first identified substrates, the acetylated lysine residues in histone proteins, it has now become evident that individual isozymes of the HDAC class have different protein targets, cellular localization, and ε-<em>N</em>-acyllysine substrate specificities. To help elucidate the activities of the different HDACs, researchers have developed a variety of peptide-based tools, providing mechanistic insights and substrate preferences of the HDACs. Due to their central regulatory roles, HDACs have been investigated as drug targets, resulting in several drugs approved for clinical use, including the naturally occurring peptide, romidepsin, spurring the interest in peptide-based inhibitors. In this review, we provide a concise overview of important discoveries enabled by peptide chemistry in the HDAC field and discuss the future potential of high-throughput peptide technologies for HDAC profiling and inhibitor discovery.</div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"33 10","pages":"Pages 1373-1386"},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148902501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}