Peptidylarginine deiminases are a family of calcium-activated enzymes with multifaceted roles in physiological and pathological processes,including in the central nervous system.Peptidylarginine deiminases cause post-...Peptidylarginine deiminases are a family of calcium-activated enzymes with multifaceted roles in physiological and pathological processes,including in the central nervous system.Peptidylarginine deiminases cause post-translational deimination/citrullination,leading to changes in structure and function of a wide range of target proteins.Deimination can facilitate protein moonlighting,modify protein-protein interaction,cause protein dysfunction and induce inflammatory responses.Peptidylarginine deiminases also regulate the biogenesis of extracellular vesicles,which play important roles in cellular communication through transfer of extracellular vesicle-cargo,e.g.,proteins and genetic material.Both peptidylarginine deiminases and extracellular vesicles are linked to a number of pathologies,including in the central nervous system,and their modulation with pharmacological peptidylarginine deiminase inhibitors have shown great promise in several in vitro and in vivo central nervous system disease models.Furthermore,extracellular vesicles derived from mesenchymal stem cells have been assessed for their therapeutic application in central nervous system injury.As circulating extracellular vesicles can be used as non-invasive liquid biopsies,their specific cargo-signatures(including deiminated proteins and microRNAs)may allow for disease“fingerprinting”and aid early central nervous system disease diagnosis,inform disease progression and response to therapy.This mini-review discusses recent advances in the field of peptidylarginine deiminase and extracellular vesicle research in the central nervous system,focusing on several central nervous system acute injury,degeneration and cancer models.展开更多
Protein citrullination involves the deimination of arginine or methylarginine resi-dues in peptide chains to form citrulline by peptidyl arginine deiminases.This process is an important protein post-translational modi...Protein citrullination involves the deimination of arginine or methylarginine resi-dues in peptide chains to form citrulline by peptidyl arginine deiminases.This process is an important protein post-translational modification that affects molecular structure and func-tion of various proteins,including histones.In recent years,protein citrullination has attracted widespread attention for its influence on gene transcription.Studies on the impact of protein citrullination modification on chromatin structure remodeling and the establishment of gene regulatory networks have made rapid progress.In this review,we briefly summarize the phys-iological functions of protein citrullination modification.Specifically,we comprehensively outline the latest progress in the study of the role of protein citrullination modification in gene transcription regulation,focusing on the interaction of protein citrullination with other post-translational modifications.展开更多
基金The work was supported in parts by a University of Westminster start-up grant to SL.
文摘Peptidylarginine deiminases are a family of calcium-activated enzymes with multifaceted roles in physiological and pathological processes,including in the central nervous system.Peptidylarginine deiminases cause post-translational deimination/citrullination,leading to changes in structure and function of a wide range of target proteins.Deimination can facilitate protein moonlighting,modify protein-protein interaction,cause protein dysfunction and induce inflammatory responses.Peptidylarginine deiminases also regulate the biogenesis of extracellular vesicles,which play important roles in cellular communication through transfer of extracellular vesicle-cargo,e.g.,proteins and genetic material.Both peptidylarginine deiminases and extracellular vesicles are linked to a number of pathologies,including in the central nervous system,and their modulation with pharmacological peptidylarginine deiminase inhibitors have shown great promise in several in vitro and in vivo central nervous system disease models.Furthermore,extracellular vesicles derived from mesenchymal stem cells have been assessed for their therapeutic application in central nervous system injury.As circulating extracellular vesicles can be used as non-invasive liquid biopsies,their specific cargo-signatures(including deiminated proteins and microRNAs)may allow for disease“fingerprinting”and aid early central nervous system disease diagnosis,inform disease progression and response to therapy.This mini-review discusses recent advances in the field of peptidylarginine deiminase and extracellular vesicle research in the central nervous system,focusing on several central nervous system acute injury,degeneration and cancer models.
基金supported by the Tianjin Synthetic Biotech-nology Innovation Capacity Improvement Project(Grant No.TSBICIP-CXRC-048).
文摘Protein citrullination involves the deimination of arginine or methylarginine resi-dues in peptide chains to form citrulline by peptidyl arginine deiminases.This process is an important protein post-translational modification that affects molecular structure and func-tion of various proteins,including histones.In recent years,protein citrullination has attracted widespread attention for its influence on gene transcription.Studies on the impact of protein citrullination modification on chromatin structure remodeling and the establishment of gene regulatory networks have made rapid progress.In this review,we briefly summarize the phys-iological functions of protein citrullination modification.Specifically,we comprehensively outline the latest progress in the study of the role of protein citrullination modification in gene transcription regulation,focusing on the interaction of protein citrullination with other post-translational modifications.