The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation.Acetylation of p53 is an important reversible enzy...The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation.Acetylation of p53 is an important reversible enzymatic process that occurs in response to DNA damage and genotoxic stress and is indispensible for p53 transcriptional activity.p53 was the first non-histone protein shown to be acetylated by histone acetyl transferases,and a number of more recent in vivo models have underscored the importance of this type of modification for p53 activity.Here,we review the current knowledge and recent findings of p53 acetylation and deacetylation and discuss the implications of these processes for the p53 pathway.展开更多
Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard t...Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard therapy for advanced PCa.In addition to its ligand androgen,accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa,especially in castration resistant prostate cancer(CRPC).To date,a number of posttranscriptional modifications of AR have been identified,including phosphorylation(e.g.by CDK1),acetylation(e.g.by p300 and recognized by BRD4),methylation(e.g.by EZH2),ubiquitination(e.g.by SPOP),and SUMOylation(e.g.by PIAS1).These modifications are essential for the maintenance of protein stability,nuclear localization and transcriptional activity of AR.This review summarizes posttranslational modifications that influence androgen-dependent and-independent activities of AR,PCa progression and therapy resistance.We further emphasize that in addition to androgen,posttranslational modification is another important way to regulate AR activity,suggesting that targeting AR posttranslational modifications,such as proteolysis targeting chimeras(PROTACs)of AR,represents a potential and promising alternate for effective treatment of CRPC.Potential areas to be investigated in the future in the field of AR posttranslational modifications are also discussed.展开更多
It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular ...It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.展开更多
The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression.The exquisite regulation of p53 functions is of vital importance for cell f...The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression.The exquisite regulation of p53 functions is of vital importance for cell fate decisions.Among the multiple layers of mechanisms controlling p53 function,posttranslational modifications (PTMs) represent an efficient and precise way.Major p53 PTMs include phosphorylation,ubiquitination,acetylation,and methylation.Meanwhile,other PTMs like sumoylation,neddylation,O-GlcNAcylation,adenosine diphosphate (ADP)-ribosylation,hydroxylation,and p-hydroxybutyrylation are also shown to play various roles in p53 regulation.By independent action or interaction,PTMs affect p53 stability,conformation,localization,and binding partners.Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases,especially in cancers.This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation.展开更多
文摘The p53 tumor suppressor is a sequence-specific transcription factor that undergoes an abundance of post-translational modifications for its regulation and activation.Acetylation of p53 is an important reversible enzymatic process that occurs in response to DNA damage and genotoxic stress and is indispensible for p53 transcriptional activity.p53 was the first non-histone protein shown to be acetylated by histone acetyl transferases,and a number of more recent in vivo models have underscored the importance of this type of modification for p53 activity.Here,we review the current knowledge and recent findings of p53 acetylation and deacetylation and discuss the implications of these processes for the p53 pathway.
基金supported by Mayo Clinic Foundation(MC-HH999 to Haojie Huang).
文摘Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard therapy for advanced PCa.In addition to its ligand androgen,accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa,especially in castration resistant prostate cancer(CRPC).To date,a number of posttranscriptional modifications of AR have been identified,including phosphorylation(e.g.by CDK1),acetylation(e.g.by p300 and recognized by BRD4),methylation(e.g.by EZH2),ubiquitination(e.g.by SPOP),and SUMOylation(e.g.by PIAS1).These modifications are essential for the maintenance of protein stability,nuclear localization and transcriptional activity of AR.This review summarizes posttranslational modifications that influence androgen-dependent and-independent activities of AR,PCa progression and therapy resistance.We further emphasize that in addition to androgen,posttranslational modification is another important way to regulate AR activity,suggesting that targeting AR posttranslational modifications,such as proteolysis targeting chimeras(PROTACs)of AR,represents a potential and promising alternate for effective treatment of CRPC.Potential areas to be investigated in the future in the field of AR posttranslational modifications are also discussed.
文摘It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.
文摘The last 40 years have witnessed how p53 rose from a viral binding protein to a central factor in both stress responses and tumor suppression.The exquisite regulation of p53 functions is of vital importance for cell fate decisions.Among the multiple layers of mechanisms controlling p53 function,posttranslational modifications (PTMs) represent an efficient and precise way.Major p53 PTMs include phosphorylation,ubiquitination,acetylation,and methylation.Meanwhile,other PTMs like sumoylation,neddylation,O-GlcNAcylation,adenosine diphosphate (ADP)-ribosylation,hydroxylation,and p-hydroxybutyrylation are also shown to play various roles in p53 regulation.By independent action or interaction,PTMs affect p53 stability,conformation,localization,and binding partners.Deregulation of the PTM-related pathway is among the major causes of p53-associated developmental disorders or diseases,especially in cancers.This review focuses on the roles of different p53 modification types and shows how these modifications are orchestrated to produce various outcomes by modulating p53 activities or targeted to treat different diseases caused by p53 dysregulation.
