E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a...E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a variety of biological processes including cell cycle regulation,proliferation and apoptosis.E3 ubiquitin ligases are often found overexpressed in human cancers,including lung cancer,and their deregulation has been shown to contribute to cancer development.However,the lack of specific inhibitors in clinical trials is a major issue in targeting E3 ubiquitin ligases with currently only one E3 ubiquitin ligase inhibitor being tested in the clinical setting.In this review,we focus on E3 ubiquitin ligases that have been found deregulated in lung cancer.Furthermore,we discuss the processes in which they are involved and evaluate them as potential anti-cancer targets.By better understanding the mechanisms by which E3 ubiquitin ligases regulate biological processes and their exact role in carcinogenesis,we can improve the development of specific E3 ubiquitin ligase inhibitors and pave the way for novel treatment strategies for cancer patients.展开更多
Protein quality control(PQC)systems play essential roles in the recognition,refolding and clearance of aberrant proteins,thus ensuring cellular protein homeostasis,or proteostasis.Especially,continued proliferation an...Protein quality control(PQC)systems play essential roles in the recognition,refolding and clearance of aberrant proteins,thus ensuring cellular protein homeostasis,or proteostasis.Especially,continued proliferation and differentiation of stem cells require a high rate of translation;therefore,accurate PQC systems are essential to maintain stem cell function.Growing evidence suggested crucial roles of PQC systems in regulating the stemness and differentiation of stem cells.This review focuses on current knowledge regarding the components of the proteostasis network in stem cells,and the importance of proteostasis in maintaining stem cell identity and regenerative functions.A complete understanding of this process might uncover potential applications in aging intervention and aging-related diseases.展开更多
Pluripotent stem cells(PSCs)can immortally self-renew in culture with a high proliferation rate,and they possess unique metabolic characteristics that facilitate pluripotency regulation.Here,we review recent progress ...Pluripotent stem cells(PSCs)can immortally self-renew in culture with a high proliferation rate,and they possess unique metabolic characteristics that facilitate pluripotency regulation.Here,we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation,with particular emphasis on pathways involving amino acid metabolism,lipid metabolism,the ubiquitin-proteasome system and autophagy.Metabolism of amino acids and lipids is tightly coupled to epigenetic modification,organelle remodeling and cell signaling pathways for pluripotency regulation.PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis.These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment.A more complete understanding of this balance will pave new ways to manipulate PSC fate.展开更多
While the cause of dopaminergic neuronal cell death in Parkinson's disease(PD)is not yet understood,many endogenous molecules have been implicated in its pathogenesis.β-phenethylamine(β-PEA),a component of vari...While the cause of dopaminergic neuronal cell death in Parkinson's disease(PD)is not yet understood,many endogenous molecules have been implicated in its pathogenesis.β-phenethylamine(β-PEA),a component of various food items including chocolate and wine,is an endogenous molecule produced from phenylalanine in the brain.It has been reported recently that long-term administration ofβ-PEA in rodents causes neurochemical and behavioral alterations similar to that produced by parkinsonian neurotoxins.The toxicity ofβ-PEA has been linked to the production of hydroxyl radical(.OH)and the generation of oxidative stress in dopaminergic areas of the brain,and this may be mediated by inhibition of mitochondrial complex-I.Another significant observation is that administration ofβ-PEA to rodents reduces striatal dopamine content and induces movement disorders similar to those of parkinsonian rodents.However,no reports are available on the extent of dopaminergic neuronal cell death after administration ofβ-PEA.Based on the literature,we set out to establishβ-PEA as an endogenous molecule that potentially contributes to the progressive development of PD.The sequence of molecular events that could be responsible for dopaminergic neuronal cell death in PD by consumption ofβ-PEA-containing foods is proposed here.Thus,long-term over-consumption of food items containingβ-PEA could be a neurological risk factor having significant pathological consequences.展开更多
文摘E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a variety of biological processes including cell cycle regulation,proliferation and apoptosis.E3 ubiquitin ligases are often found overexpressed in human cancers,including lung cancer,and their deregulation has been shown to contribute to cancer development.However,the lack of specific inhibitors in clinical trials is a major issue in targeting E3 ubiquitin ligases with currently only one E3 ubiquitin ligase inhibitor being tested in the clinical setting.In this review,we focus on E3 ubiquitin ligases that have been found deregulated in lung cancer.Furthermore,we discuss the processes in which they are involved and evaluate them as potential anti-cancer targets.By better understanding the mechanisms by which E3 ubiquitin ligases regulate biological processes and their exact role in carcinogenesis,we can improve the development of specific E3 ubiquitin ligase inhibitors and pave the way for novel treatment strategies for cancer patients.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100)the National Key Research and Development Program of China(2018YFC2000100)the National Natural Science Foundation of China(81625009,81921006,81822018).
文摘Protein quality control(PQC)systems play essential roles in the recognition,refolding and clearance of aberrant proteins,thus ensuring cellular protein homeostasis,or proteostasis.Especially,continued proliferation and differentiation of stem cells require a high rate of translation;therefore,accurate PQC systems are essential to maintain stem cell function.Growing evidence suggested crucial roles of PQC systems in regulating the stemness and differentiation of stem cells.This review focuses on current knowledge regarding the components of the proteostasis network in stem cells,and the importance of proteostasis in maintaining stem cell identity and regenerative functions.A complete understanding of this process might uncover potential applications in aging intervention and aging-related diseases.
基金This research was funded by grants from the National Key R&D Program of China 2018YFA0108402,the Strategic Priority Research Program of the Chinese Academy of Sciences XDA16030302the National Natural Science Foundation of China Program 31720103907,31621004,31570995+1 种基金the Key Research Program of the Chinese Academy of Sciences ZDRW-ZS-2017-5 to T.Zthe Strategic Priority Research Program of the Chinese Academy of Science XDA16040501 to J.C and the China Postdoctoral Science Foundation(2018M630205)to K.L.
文摘Pluripotent stem cells(PSCs)can immortally self-renew in culture with a high proliferation rate,and they possess unique metabolic characteristics that facilitate pluripotency regulation.Here,we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation,with particular emphasis on pathways involving amino acid metabolism,lipid metabolism,the ubiquitin-proteasome system and autophagy.Metabolism of amino acids and lipids is tightly coupled to epigenetic modification,organelle remodeling and cell signaling pathways for pluripotency regulation.PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis.These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment.A more complete understanding of this balance will pave new ways to manipulate PSC fate.
文摘While the cause of dopaminergic neuronal cell death in Parkinson's disease(PD)is not yet understood,many endogenous molecules have been implicated in its pathogenesis.β-phenethylamine(β-PEA),a component of various food items including chocolate and wine,is an endogenous molecule produced from phenylalanine in the brain.It has been reported recently that long-term administration ofβ-PEA in rodents causes neurochemical and behavioral alterations similar to that produced by parkinsonian neurotoxins.The toxicity ofβ-PEA has been linked to the production of hydroxyl radical(.OH)and the generation of oxidative stress in dopaminergic areas of the brain,and this may be mediated by inhibition of mitochondrial complex-I.Another significant observation is that administration ofβ-PEA to rodents reduces striatal dopamine content and induces movement disorders similar to those of parkinsonian rodents.However,no reports are available on the extent of dopaminergic neuronal cell death after administration ofβ-PEA.Based on the literature,we set out to establishβ-PEA as an endogenous molecule that potentially contributes to the progressive development of PD.The sequence of molecular events that could be responsible for dopaminergic neuronal cell death in PD by consumption ofβ-PEA-containing foods is proposed here.Thus,long-term over-consumption of food items containingβ-PEA could be a neurological risk factor having significant pathological consequences.