Active endogenous metabolites regulate the viability of cells. This process is controlled by a series ofinteractions between small metabolites and large proteins. Previously, several studies had reported thatmetabolit...Active endogenous metabolites regulate the viability of cells. This process is controlled by a series ofinteractions between small metabolites and large proteins. Previously, several studies had reported thatmetabolite regulates the protein functions, such as diacylglycerol to protein kinase C, lactose regulationof the lac repressor, and HIF-1α stabilization by 2-hydroxyglutarate. However, decades old traditionalbiochemical methods are insufficient to systematically investigate the bio-molecular reactions for a high-throughput discovery. Here, we have reviewed an update on the recently developed chemical proteomicscalled activity-based protein profiling （ABPP）. ABPP is able to identify proteins interacted eithercovalently or non-covalently with metabolites significantly. Thus, ABPP will facilitate the characteriza-tion of specific metabolite regulating; proteins in human disease progression.展开更多
Protein-metabolite interactions(PMIs)play important roles in various biological processes,especially in disease progression.However,due to the complexity of living cells,it is very difficult to identify specific PMIs....Protein-metabolite interactions(PMIs)play important roles in various biological processes,especially in disease progression.However,due to the complexity of living cells,it is very difficult to identify specific PMIs.Herein,we chose one oncogenic factor,metadherin(MTDH),as a bait to identify its in vivo interacting metabolites in cancer cells.Cholesterol is an important metabolite and essential structural component of cell membranes.It could also drive several diseases including cancer.Interestingly,we found that cholesterol robustly interacted with MTDH and downregulated the expression of MTDH in cancer cells.Furthermore,MTDH disturbed metabolite alterations under cholesterol treatment in MTDH transduced cancer cells.Collectively,our results uncover an undescribed PMI where MTDH,as an oncogenic factor,might positively regulate cancer progression by interacting with choleste rol.This study interprets the theoretical basis of PMI-oriented cancer progression and targeting therapies in clinic.展开更多
基金supported by the National Natural Science Foundation of China(No.81672440)Innovation Program of Science and Research from the DICP,CAS(No.DICP TMSR201601)the 100 Talents Program of Chinese Academy of Sciences
文摘Active endogenous metabolites regulate the viability of cells. This process is controlled by a series ofinteractions between small metabolites and large proteins. Previously, several studies had reported thatmetabolite regulates the protein functions, such as diacylglycerol to protein kinase C, lactose regulationof the lac repressor, and HIF-1α stabilization by 2-hydroxyglutarate. However, decades old traditionalbiochemical methods are insufficient to systematically investigate the bio-molecular reactions for a high-throughput discovery. Here, we have reviewed an update on the recently developed chemical proteomicscalled activity-based protein profiling （ABPP）. ABPP is able to identify proteins interacted eithercovalently or non-covalently with metabolites significantly. Thus, ABPP will facilitate the characteriza-tion of specific metabolite regulating; proteins in human disease progression.
基金the National Natural Science Foundation of China(Nos.81672440,21575142)Innovation Program of Science and Research from the DICP,CAS(No.DICP ZZBS201803)。
文摘Protein-metabolite interactions(PMIs)play important roles in various biological processes,especially in disease progression.However,due to the complexity of living cells,it is very difficult to identify specific PMIs.Herein,we chose one oncogenic factor,metadherin(MTDH),as a bait to identify its in vivo interacting metabolites in cancer cells.Cholesterol is an important metabolite and essential structural component of cell membranes.It could also drive several diseases including cancer.Interestingly,we found that cholesterol robustly interacted with MTDH and downregulated the expression of MTDH in cancer cells.Furthermore,MTDH disturbed metabolite alterations under cholesterol treatment in MTDH transduced cancer cells.Collectively,our results uncover an undescribed PMI where MTDH,as an oncogenic factor,might positively regulate cancer progression by interacting with choleste rol.This study interprets the theoretical basis of PMI-oriented cancer progression and targeting therapies in clinic.
