Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions like whether the methylation marks themselves are faithfully transmit- ted into daughter...Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions like whether the methylation marks themselves are faithfully transmit- ted into daughter cells and through what mechanisms are currently under active investigation. Previ- ously, methylation was considered to be irreversible, but the recent discovery of histone lysine de- methylases revealed a dynamic nature of histone methylation regulation on four of the main sites of methylation on histone H3 and H4 tails (H3K4, H3K9, H3K27 and H3K36). Even so, it is still unclear whether demethylases specific for the remaining two sites, H3K79 and H4K20, exist. Furthermore, be- sides histone proteins, the lysine methylation and demethylation also occur on non-histone proteins, which are probably subjected to similar regulation as histones. This review discusses recent pro- gresses in protein lysine methylation regulation focusing on the above topics, while referring readers to a number of recent reviews for the biochemistry and biology of these enzymes.展开更多
Lysine acetylation, an evolutionarily conserved post-translational protein modification, is reversibly catalyzed by lysine acetyltransferases and lysine deacetylases. Lysine acetylation, which was first discovered on ...Lysine acetylation, an evolutionarily conserved post-translational protein modification, is reversibly catalyzed by lysine acetyltransferases and lysine deacetylases. Lysine acetylation, which was first discovered on histones, mainly functions to configure the structure of chromatin and regulate gene transcriptional activity. Over the past decade, with advances in high-resolution mass spectrometry, a vast and growing number of non-histone proteins modified by acetylation in various plant species have been identified.Lysine acetylation of non-histone proteins is widely involved in regulating biological processes in plants such as photosynthesis, energy metabolism, hormone signal transduction and stress responses. Moreover, in plants, lysine acetylation plays crucial roles in regulating enzyme activity,protein stability, protein interaction and subcellular localization. This review summarizes recent progress in our understanding of the biological functions and mechanisms of non-histone protein acetylation in plants. Research prospects in this field are also noted.展开更多
Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein ...Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.展开更多
Lactylation is one of the post-translational modifications of proteins,a process in which lactyl residues bind to the lysine residues of proteins.This modification can alter the structure,stability,and function of pro...Lactylation is one of the post-translational modifications of proteins,a process in which lactyl residues bind to the lysine residues of proteins.This modification can alter the structure,stability,and function of proteins,which in turn regulates cellular metabolism,aging,and the onset of disease.This review classifies proteins with lactylation effects into histones and non-histone proteins and analyzes their functional roles when lactylation occurs.The in-depth exploration of lactylation is still in its infancy,and many aspects of its regulation,functional significance and therapeutic potential need to be further explored.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal neoplasms worldwide and represents the vast majority of pancreatic cancer cases.Understanding the molecular pathogenesis and the underlying mechanisms in...Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal neoplasms worldwide and represents the vast majority of pancreatic cancer cases.Understanding the molecular pathogenesis and the underlying mechanisms involved in the initiation,maintenance,and progression of PDAC is an urgent need,which may lead to the development of novel therapeutic strategies against this deadly cancer.Here,we review the role of SET and MYND domaincontaining protein 2(SMYD2)in initiating and maintaining PDAC development through methylating multiple tumor suppressors and oncogenic proteins.Given the broad substrate specificity of SMYD2 and its involvement in diverse oncogenic signaling pathways in many other cancers,the mechanistic extrapolation of SMYD2 from these cancers to PDAC may allow for developing new hypotheses about the mechanisms driving PDAC tumor growth and metastasis,supporting a proposition that targeting SMYD2 could be a powerful strategy for the prevention and treatment of PDAC.展开更多
Flaviviruses are a group of positive-stranded RNA viruses that cause a broad spectrum of severe illnesses in humans worldwide.Clinical manifestations of flavivirus infections range from mild febrile illness to hemorrh...Flaviviruses are a group of positive-stranded RNA viruses that cause a broad spectrum of severe illnesses in humans worldwide.Clinical manifestations of flavivirus infections range from mild febrile illness to hemorrhage,shock,and neurological manifestations.Flavivirus infections cause a substantial global health impact,with an estimated more than 400 million cases of infections annually.Hence,an understanding of flavivirus-host interaction is urgently needed for new antiviral therapeutic strategies.In recent years,many aspects concerning epigenetic therapy for viral infections have been addressed,including methylation of the genome,acetylation/deacetylation of histone complex and microRNA regulation.In this context,we surveyed and reviewed the literature and summarized the epigenetic effects of resveratrol,a natural polyphenol with potential anti-viral properties,on flavivirus infections.展开更多
The purpose of this study was to analyze spatio-temporal dynamics of localization of protease-sensitive sites Arg-X in non-histone and histone blocks of heteropolymer suprastructures （nucleoplasm, chromatin, nuclear ...The purpose of this study was to analyze spatio-temporal dynamics of localization of protease-sensitive sites Arg-X in non-histone and histone blocks of heteropolymer suprastructures （nucleoplasm, chromatin, nuclear matrix） as possible zones affecting the conformational rearrangements of the total interphase chromatin at the induction of increasing morphogenesis of mature embryos-germs of spring and transformed from its winter wheat. Germinated embryos-germs were detached from endosperm after 24 hours from the start of soaking. Cell nuclei have been allocated from embryos-germs and cleared, and then from their heteropolymer suprastructures （nucleoplasm, chromatin loosely bound with nuclear matrix and chromatin tightly bound with nuclear matrix, and nuclear matrix） were extracted by increasing ionic strength of solution. From isolated nuclear suprastructures, non-histone proteins were separated from histones using ion exchange chromatography. Trypsin-like complexes from non-histone proteins and histone blocks were isolated using the affinity chromatography. The Arg-X （tryptase） activity was assessed by cleavage of Arg-X bonds in the arginine-enriched protein protamine. Hypersensitivity to the Arg-X proteolysis in trypsin-like complexes detected at the level suprastructures of chromatin tightly bound with the nuclear matrix was shown. The most active changes of the nuclear proteome have occurred at the level of the non-histone proteins and the core histones （H2A ＋ H2B） （H3 ＋ H4） of induced to growth embryos-seedlings of winter wheat （compared to the initial spring form of wheat）. Perhaps hypersensitivity to the Arg-X activity of the trypsin-like complexes in the non-histone proteins and the core blocks of chromatin tightly bound with nuclear matrix have been entrenched during the transforming of the winter wheat from the initial spring wheat.展开更多
文摘Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions like whether the methylation marks themselves are faithfully transmit- ted into daughter cells and through what mechanisms are currently under active investigation. Previ- ously, methylation was considered to be irreversible, but the recent discovery of histone lysine de- methylases revealed a dynamic nature of histone methylation regulation on four of the main sites of methylation on histone H3 and H4 tails (H3K4, H3K9, H3K27 and H3K36). Even so, it is still unclear whether demethylases specific for the remaining two sites, H3K79 and H4K20, exist. Furthermore, be- sides histone proteins, the lysine methylation and demethylation also occur on non-histone proteins, which are probably subjected to similar regulation as histones. This review discusses recent pro- gresses in protein lysine methylation regulation focusing on the above topics, while referring readers to a number of recent reviews for the biochemistry and biology of these enzymes.
基金supported by grants from the National Natural Science Foundation of China (No. 32070551 and No. 32371326)the Youth Innovation Promotion Association, CAS (No. 201860)Key Research Program of Frontier Sciences, Chinese Academy of Sciences (ZDBS-LY-SM009)。
文摘Lysine acetylation, an evolutionarily conserved post-translational protein modification, is reversibly catalyzed by lysine acetyltransferases and lysine deacetylases. Lysine acetylation, which was first discovered on histones, mainly functions to configure the structure of chromatin and regulate gene transcriptional activity. Over the past decade, with advances in high-resolution mass spectrometry, a vast and growing number of non-histone proteins modified by acetylation in various plant species have been identified.Lysine acetylation of non-histone proteins is widely involved in regulating biological processes in plants such as photosynthesis, energy metabolism, hormone signal transduction and stress responses. Moreover, in plants, lysine acetylation plays crucial roles in regulating enzyme activity,protein stability, protein interaction and subcellular localization. This review summarizes recent progress in our understanding of the biological functions and mechanisms of non-histone protein acetylation in plants. Research prospects in this field are also noted.
基金supported by Applied Basic Research Joint Fund Project of Yunnan Province,No.202301AY070001-200Middle-aged Academic and Technical Training Project for High-Level Talents,No.202105AC160065+1 种基金Yunnan Clinical Medical Center for Neurological and Cardiovascular Diseases,No.YWLCYXZX2023300077Key Clinical Specialty of Neurology in Yunnan Province,No.300064(all to CL)。
文摘Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.
基金supported by the Natural Science Foundation of Guangdong Province(No.2024A1515010605,2022A1515140034)Discipline Construction Project of Guangdong Medical University(No.4SG24007G,4SG22302P)+1 种基金Medical Scientific Research Fund of Guangdong Province(No.B2024193)Dongguan Social Development and Scientific Technology Project,China(No.20231800936562).
文摘Lactylation is one of the post-translational modifications of proteins,a process in which lactyl residues bind to the lysine residues of proteins.This modification can alter the structure,stability,and function of proteins,which in turn regulates cellular metabolism,aging,and the onset of disease.This review classifies proteins with lactylation effects into histones and non-histone proteins and analyzes their functional roles when lactylation occurs.The in-depth exploration of lactylation is still in its infancy,and many aspects of its regulation,functional significance and therapeutic potential need to be further explored.
文摘Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal neoplasms worldwide and represents the vast majority of pancreatic cancer cases.Understanding the molecular pathogenesis and the underlying mechanisms involved in the initiation,maintenance,and progression of PDAC is an urgent need,which may lead to the development of novel therapeutic strategies against this deadly cancer.Here,we review the role of SET and MYND domaincontaining protein 2(SMYD2)in initiating and maintaining PDAC development through methylating multiple tumor suppressors and oncogenic proteins.Given the broad substrate specificity of SMYD2 and its involvement in diverse oncogenic signaling pathways in many other cancers,the mechanistic extrapolation of SMYD2 from these cancers to PDAC may allow for developing new hypotheses about the mechanisms driving PDAC tumor growth and metastasis,supporting a proposition that targeting SMYD2 could be a powerful strategy for the prevention and treatment of PDAC.
基金funding from the Ministry of Higher Education,Malaysia for niche area research under the Higher Institution Centre of Excellence(HICoE)program(MO002-2019&TIDREC-2023).
文摘Flaviviruses are a group of positive-stranded RNA viruses that cause a broad spectrum of severe illnesses in humans worldwide.Clinical manifestations of flavivirus infections range from mild febrile illness to hemorrhage,shock,and neurological manifestations.Flavivirus infections cause a substantial global health impact,with an estimated more than 400 million cases of infections annually.Hence,an understanding of flavivirus-host interaction is urgently needed for new antiviral therapeutic strategies.In recent years,many aspects concerning epigenetic therapy for viral infections have been addressed,including methylation of the genome,acetylation/deacetylation of histone complex and microRNA regulation.In this context,we surveyed and reviewed the literature and summarized the epigenetic effects of resveratrol,a natural polyphenol with potential anti-viral properties,on flavivirus infections.
文摘The purpose of this study was to analyze spatio-temporal dynamics of localization of protease-sensitive sites Arg-X in non-histone and histone blocks of heteropolymer suprastructures （nucleoplasm, chromatin, nuclear matrix） as possible zones affecting the conformational rearrangements of the total interphase chromatin at the induction of increasing morphogenesis of mature embryos-germs of spring and transformed from its winter wheat. Germinated embryos-germs were detached from endosperm after 24 hours from the start of soaking. Cell nuclei have been allocated from embryos-germs and cleared, and then from their heteropolymer suprastructures （nucleoplasm, chromatin loosely bound with nuclear matrix and chromatin tightly bound with nuclear matrix, and nuclear matrix） were extracted by increasing ionic strength of solution. From isolated nuclear suprastructures, non-histone proteins were separated from histones using ion exchange chromatography. Trypsin-like complexes from non-histone proteins and histone blocks were isolated using the affinity chromatography. The Arg-X （tryptase） activity was assessed by cleavage of Arg-X bonds in the arginine-enriched protein protamine. Hypersensitivity to the Arg-X proteolysis in trypsin-like complexes detected at the level suprastructures of chromatin tightly bound with the nuclear matrix was shown. The most active changes of the nuclear proteome have occurred at the level of the non-histone proteins and the core histones （H2A ＋ H2B） （H3 ＋ H4） of induced to growth embryos-seedlings of winter wheat （compared to the initial spring form of wheat）. Perhaps hypersensitivity to the Arg-X activity of the trypsin-like complexes in the non-histone proteins and the core blocks of chromatin tightly bound with nuclear matrix have been entrenched during the transforming of the winter wheat from the initial spring wheat.
