Metabolic reprogramming plays a central role in tumors.However,the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood.Here,we try to identify the mechanism by which histone acety...Metabolic reprogramming plays a central role in tumors.However,the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood.Here,we try to identify the mechanism by which histone acetyltransferase 1(HAT1)confers reprogramming of gluconeogenesis/lipogenesis in liver cancer.Diethylnitrosamine(DEN)/carbon tetrachloride(CCl4)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice.Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver.Protein phosphatase 2 scaffold subunit alpha(PPP2R1A)promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1(PCK1)serine 90 dephosphorylation to suppress the tumor growth.HAT1 succinylated PPP2R1A at lysine 541(K541)to block the assembly of protein phosphatase 2A(PP2A)holoenzyme and interaction with PCK1,resulting in the depression of dephosphorylation of PCK1.HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation,leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1(SREBP1)nuclear accumulation-induced lipogenesis gene expression,which enhanced the tumor growth.In conclusion,succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer.Our finding provides new insights into the mechanism by which post-translational modifications(PTMs)confer the conversion of tumor suppressor function to oncogene.展开更多
As data presentation,in October,2017,the total retail sales of consumer goods reaches RMB3424.1 billion,a year-on-year increase of 10%.Thereinto,the consumer goods turnover of the above norm units is RMB 1437.4 billio...As data presentation,in October,2017,the total retail sales of consumer goods reaches RMB3424.1 billion,a year-on-year increase of 10%.Thereinto,the consumer goods turnover of the above norm units is RMB 1437.4 billion with an increase of 7.2%.From January to October in 2017,the total retail sales of social consumer goods reaches RMB 29741.9billion,展开更多
Let(X, d, μ) be a metric measure space satisfying both the upper doubling and the geometrically doubling conditions in the sense of Hyt?nen. In this paper, the authors obtain the boundedness of the commutators of θ-...Let(X, d, μ) be a metric measure space satisfying both the upper doubling and the geometrically doubling conditions in the sense of Hyt?nen. In this paper, the authors obtain the boundedness of the commutators of θ-type Calderón-Zygmund operators with RBMO functions from L∞(μ) into RBMO(μ) and from Hat1,∞(μ) into L1(μ), respectively.As a consequence of these results, they establish the Lp(μ) boundedness of the commutators on the non-homogeneous metric spaces.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82103066,82372818,82303210,and 82302887)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-009A,China).
文摘Metabolic reprogramming plays a central role in tumors.However,the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood.Here,we try to identify the mechanism by which histone acetyltransferase 1(HAT1)confers reprogramming of gluconeogenesis/lipogenesis in liver cancer.Diethylnitrosamine(DEN)/carbon tetrachloride(CCl4)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice.Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver.Protein phosphatase 2 scaffold subunit alpha(PPP2R1A)promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1(PCK1)serine 90 dephosphorylation to suppress the tumor growth.HAT1 succinylated PPP2R1A at lysine 541(K541)to block the assembly of protein phosphatase 2A(PP2A)holoenzyme and interaction with PCK1,resulting in the depression of dephosphorylation of PCK1.HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation,leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1(SREBP1)nuclear accumulation-induced lipogenesis gene expression,which enhanced the tumor growth.In conclusion,succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer.Our finding provides new insights into the mechanism by which post-translational modifications(PTMs)confer the conversion of tumor suppressor function to oncogene.
文摘As data presentation,in October,2017,the total retail sales of consumer goods reaches RMB3424.1 billion,a year-on-year increase of 10%.Thereinto,the consumer goods turnover of the above norm units is RMB 1437.4 billion with an increase of 7.2%.From January to October in 2017,the total retail sales of social consumer goods reaches RMB 29741.9billion,
基金supported by the National Natural Science Foundation of China(No.11671414)
文摘Let(X, d, μ) be a metric measure space satisfying both the upper doubling and the geometrically doubling conditions in the sense of Hyt?nen. In this paper, the authors obtain the boundedness of the commutators of θ-type Calderón-Zygmund operators with RBMO functions from L∞(μ) into RBMO(μ) and from Hat1,∞(μ) into L1(μ), respectively.As a consequence of these results, they establish the Lp(μ) boundedness of the commutators on the non-homogeneous metric spaces.
