Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulatio...Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. We hypothesized and were going to identify that the regulatory function of PCBP1 is performed through different complexes of proteins that include PCBP1. Methods:To test our hypothesis,approaches of protein wal-king with a yeast two-hybrid system (Y2H),pulling down in yeasts,co-immunoprecipitation and immunofluorescent microscopy assay were employed in this study. The PCBP1 was used as the initial "walker" to search for its interaction partner(s). Results:Candidate proteins including MYL6,PECAM1,CSH1,RAB7,p57KIP2,ACTG1,RBMS1 and PSG4-like were identified with selection mediums and preceding methods. Conclusion:With these candidate protein molecules,some protein complexes associating with PCBP1 are proposed,which may help in a better understanding of physiological functions of PCBP1 and proved evidence that PCBP1 is involved in variant biological pathways.展开更多
Hypoxic-ischemic encephalopathy（HIE） is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-isch...Hypoxic-ischemic encephalopathy（HIE） is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release,cellular proteolysis,reactive oxygen species generation,nitric oxide synthesis,and inflammation.The molecular and cellular changes in HIE include protein misfolding,aggregation,and destruction of organelles.The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway,the extrinsic Fas receptor pathway,and the endoplasmic reticulum stress-induced pathway.Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century.Hypothermia,xenon gas treatment,the use of melatonin and erythropoietin,and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes.A large number of molecular chaperones are induced after brain ischemia and hypoxia,among which the heat shock proteins are the most important.Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects.Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations,assisting in the proper folding of newly synthesized polypeptides,regulating the degradation of misfolded proteins,inhibiting the aggregation of proteins,and by controlling the refolding of misfolded proteins.In addition,heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways,including the intrinsic pathway,the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway.Molecular chaperones play a key role in neuroprotection in HIE.In this review,we provide an overview of the mechanisms of HIE and discuss the various treatment strategies.Given their critical role in the disease,molecular chaperones are promising therapeutic targets for HIE.展开更多
基金Supported in part by the “985” program(985-2-035-39) of the Chinese Ministry of Education“973” project(2007CB511902)of the Chinese Ministry of Sciences and Technology+1 种基金National Nature Science Foundation(30671157)the NewYork State Office of Mental Retardation and Developmental Disabilities(NYSOMRDD)~~
文摘Objective:PCBP1 is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. The protein plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. We hypothesized and were going to identify that the regulatory function of PCBP1 is performed through different complexes of proteins that include PCBP1. Methods:To test our hypothesis,approaches of protein wal-king with a yeast two-hybrid system (Y2H),pulling down in yeasts,co-immunoprecipitation and immunofluorescent microscopy assay were employed in this study. The PCBP1 was used as the initial "walker" to search for its interaction partner(s). Results:Candidate proteins including MYL6,PECAM1,CSH1,RAB7,p57KIP2,ACTG1,RBMS1 and PSG4-like were identified with selection mediums and preceding methods. Conclusion:With these candidate protein molecules,some protein complexes associating with PCBP1 are proposed,which may help in a better understanding of physiological functions of PCBP1 and proved evidence that PCBP1 is involved in variant biological pathways.
文摘Hypoxic-ischemic encephalopathy（HIE） is a disease that occurs when the brain is subjected to hypoxia,resulting in neuronal death and neurological deficits,with a poor prognosis.The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release,cellular proteolysis,reactive oxygen species generation,nitric oxide synthesis,and inflammation.The molecular and cellular changes in HIE include protein misfolding,aggregation,and destruction of organelles.The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway,the extrinsic Fas receptor pathway,and the endoplasmic reticulum stress-induced pathway.Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century.Hypothermia,xenon gas treatment,the use of melatonin and erythropoietin,and hypoxic-ischemic preconditioning have proven effective in HIE patients.Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes.A large number of molecular chaperones are induced after brain ischemia and hypoxia,among which the heat shock proteins are the most important.Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects.Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations,assisting in the proper folding of newly synthesized polypeptides,regulating the degradation of misfolded proteins,inhibiting the aggregation of proteins,and by controlling the refolding of misfolded proteins.In addition,heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways,including the intrinsic pathway,the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway.Molecular chaperones play a key role in neuroprotection in HIE.In this review,we provide an overview of the mechanisms of HIE and discuss the various treatment strategies.Given their critical role in the disease,molecular chaperones are promising therapeutic targets for HIE.
