Protein post-translational modifications (PTMs) represent essential regulatory mechanisms to diversify the function of proteins. Intracellular reactive moieties such as phosphoryl, glycosyl, or acyl group are transferred to the target proteins and form a covalent bond with the side chain of specific amino acids, usually in a transferase-dependent manner. This leads to specific changes in protein conformation, subcellular localization and stability. Compared to transcriptional and translational regulations, PTMs take place on preexisting proteins and are much faster as a response mechanism to cellular and environmental cues. Through PTMs, the proteomic network is reconstructed from a comparatively stationary and isolated status, to the more dynamic and programmable signaling cascades. Therefore, PTMs play fundamental roles in shaping signaling networks and dysregulation of these reactions underlines the mechanism of almost all kinds of diseases, including but not limited to cancer, metabolic disorders and neurodegenerative diseases.
Over the decades, more than 300 PTMs have been discovered across eukaryotes and prokaryotes. Among them, “hot” modifications like phosphorylation, ubiquitination, methylation, acetylation, and glycosylation have been extensively investigated and each of them reveals profound impacts on cell fate decision and maintenance of cell identity. However, given the complexity of intracellular reactive moieties, one could imagine that these PTMs probably represent just the tip of the iceberg. In fact, many other PTMs remain uncharacterized mainly because of technical challenges for relevant investigations. Some of the prominent examples include lysine-based non-acetyl short-chain acylation, long-chain lipidation, and ribosome-independent amino acid incorporation, all of which appear to possess essential physiological roles. The studies of these three “cold” PTMs, although still less developed, similarly entered an explosive phase in the very recent years thanks to the advances in techniques for detection and manipulation. However, systematic coverage for these three “up-and-coming” research areas is still missing in the scientific community. Another interesting common ground between these three PTMs is that their precursor modifiers are important intermediate metabolites. Therefore, it is plausible that those PTMs confer the ability to sense metabolic status, and bridge metabolome with either cellular transcriptome via histone modifications or with proteome via direct modifications of non-histone proteins. These important scientific questions have not been sufficiently addressed and will be the focus of this collection.
In this Research Topic, we welcome contributions addressing the biology, physiology and pathology of lysine-based non-acetyl acylation, long-chain lipidation as well as ribosome-independent amino acid incorporation. Coverage for other less-known PTMs will be considered based on the significance and novelty of the topic. The following article types are welcome: Original Research, Review or Mini Review, Perspective and Methods.
In particular, we welcome contributions that cover the following topics:
• Identification of novel modifications;
• Molecular machinery underlying existing modifications;
• Metabolic regulation of the understudied PTMs;
• The function of lysine-based non-acetyl acylation, long-chain lipidation, and arginylation in tissue homeostasis and pathogenesis;
• CoA biology in physiology and pathology;
• Newly developed methodologies to investigate acylation or other understudied PTMs.
Protein post-translational modifications (PTMs) represent essential regulatory mechanisms to diversify the function of proteins. Intracellular reactive moieties such as phosphoryl, glycosyl, or acyl group are transferred to the target proteins and form a covalent bond with the side chain of specific amino acids, usually in a transferase-dependent manner. This leads to specific changes in protein conformation, subcellular localization and stability. Compared to transcriptional and translational regulations, PTMs take place on preexisting proteins and are much faster as a response mechanism to cellular and environmental cues. Through PTMs, the proteomic network is reconstructed from a comparatively stationary and isolated status, to the more dynamic and programmable signaling cascades. Therefore, PTMs play fundamental roles in shaping signaling networks and dysregulation of these reactions underlines the mechanism of almost all kinds of diseases, including but not limited to cancer, metabolic disorders and neurodegenerative diseases.
Over the decades, more than 300 PTMs have been discovered across eukaryotes and prokaryotes. Among them, “hot” modifications like phosphorylation, ubiquitination, methylation, acetylation, and glycosylation have been extensively investigated and each of them reveals profound impacts on cell fate decision and maintenance of cell identity. However, given the complexity of intracellular reactive moieties, one could imagine that these PTMs probably represent just the tip of the iceberg. In fact, many other PTMs remain uncharacterized mainly because of technical challenges for relevant investigations. Some of the prominent examples include lysine-based non-acetyl short-chain acylation, long-chain lipidation, and ribosome-independent amino acid incorporation, all of which appear to possess essential physiological roles. The studies of these three “cold” PTMs, although still less developed, similarly entered an explosive phase in the very recent years thanks to the advances in techniques for detection and manipulation. However, systematic coverage for these three “up-and-coming” research areas is still missing in the scientific community. Another interesting common ground between these three PTMs is that their precursor modifiers are important intermediate metabolites. Therefore, it is plausible that those PTMs confer the ability to sense metabolic status, and bridge metabolome with either cellular transcriptome via histone modifications or with proteome via direct modifications of non-histone proteins. These important scientific questions have not been sufficiently addressed and will be the focus of this collection.
In this Research Topic, we welcome contributions addressing the biology, physiology and pathology of lysine-based non-acetyl acylation, long-chain lipidation as well as ribosome-independent amino acid incorporation. Coverage for other less-known PTMs will be considered based on the significance and novelty of the topic. The following article types are welcome: Original Research, Review or Mini Review, Perspective and Methods.
In particular, we welcome contributions that cover the following topics:
• Identification of novel modifications;
• Molecular machinery underlying existing modifications;
• Metabolic regulation of the understudied PTMs;
• The function of lysine-based non-acetyl acylation, long-chain lipidation, and arginylation in tissue homeostasis and pathogenesis;
• CoA biology in physiology and pathology;
• Newly developed methodologies to investigate acylation or other understudied PTMs.
