Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by...Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM 1) located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.展开更多
The sirtuin proteins constitute class III histone deacetylases (HDACs). These evolutionarily conserved NAD+-dependent enzymes form an important component in a variety of cellular and biological processes with highl...The sirtuin proteins constitute class III histone deacetylases (HDACs). These evolutionarily conserved NAD+-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in pro- moting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.展开更多
Effects of La<sup>9</sup>3+) and Gd<sup>3+</sup> on Ca<sup>2+</sup> influx were investigated in rat hepatoma H-35 cells by measuring the initial rate of<sup>45</sup>Ca&l...Effects of La<sup>9</sup>3+) and Gd<sup>3+</sup> on Ca<sup>2+</sup> influx were investigated in rat hepatoma H-35 cells by measuring the initial rate of<sup>45</sup>Ca<sup>2+</sup> uptake. It was found that the maximum initial rate of Ca<sup>2+</sup> uptake was increased six- to ten-fold at low concentrations of La<sup>3+</sup> and Gd<sup>3+</sup>. Kinetic analyses by measuring the initial rate of Ca<sup>2+</sup> influx at different external Ca<sup>2+</sup> concentrations indicated the existence of two intracellular exchangeable components in the basal Ca<sup>2+</sup> system, with low and high affinities for Ca<sup>2+</sup>,and only one class of Ca<sup>2+</sup> binding sites was observed in the La<sup>3+</sup>- or Gd<sup>3+</sup>-treated cells. For high affinity, La<sup>3+</sup> and Gd<sup>3+</sup> increased both kinetic parameters K<sub>m</sub> and V<sub>(</sub>max of basal Ca<sup>2+</sup> influx. La<sup>3+</sup> and Gd<sup>3+</sup> compete directly with Ca<sup>2+</sup> for Ca<sup>2+</sup> binding site for low affinity. The kinetics is competitive.展开更多
The principles and molecular mechanisms underlying biological pattern formation are difficult to elucidate in most cases due to the overwhelming physiologic complexity associated with the natural context. The understa...The principles and molecular mechanisms underlying biological pattern formation are difficult to elucidate in most cases due to the overwhelming physiologic complexity associated with the natural context. The understanding of a particular mechanism, not to speak of underlying universal principles, is difficult due to the diversity and uncertainty of the biological systems. Although current genetic and biochemical approaches have greatly advanced our understanding of pattern formation, the progress mainly relies on experimental phenotypes obtained from time- consuming studies of gain or loss of function mutants. It is prevailingly considered that synthetic biology will come to the application age, but more importantly synthetic biology can be used to understand the life. Using periodic stripe pattern formation as a paradigm, we discuss how to apply synthetic biology in understanding biological pattern formation and hereafter foster the applications like tissue engineering.展开更多
文摘Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome (SARS) coronavirus M protein suppresses type I interferon (IFN) production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain (TM 1) located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.
文摘The sirtuin proteins constitute class III histone deacetylases (HDACs). These evolutionarily conserved NAD+-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in pro- moting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.
文摘Effects of La<sup>9</sup>3+) and Gd<sup>3+</sup> on Ca<sup>2+</sup> influx were investigated in rat hepatoma H-35 cells by measuring the initial rate of<sup>45</sup>Ca<sup>2+</sup> uptake. It was found that the maximum initial rate of Ca<sup>2+</sup> uptake was increased six- to ten-fold at low concentrations of La<sup>3+</sup> and Gd<sup>3+</sup>. Kinetic analyses by measuring the initial rate of Ca<sup>2+</sup> influx at different external Ca<sup>2+</sup> concentrations indicated the existence of two intracellular exchangeable components in the basal Ca<sup>2+</sup> system, with low and high affinities for Ca<sup>2+</sup>,and only one class of Ca<sup>2+</sup> binding sites was observed in the La<sup>3+</sup>- or Gd<sup>3+</sup>-treated cells. For high affinity, La<sup>3+</sup> and Gd<sup>3+</sup> increased both kinetic parameters K<sub>m</sub> and V<sub>(</sub>max of basal Ca<sup>2+</sup> influx. La<sup>3+</sup> and Gd<sup>3+</sup> compete directly with Ca<sup>2+</sup> for Ca<sup>2+</sup> binding site for low affinity. The kinetics is competitive.
文摘The principles and molecular mechanisms underlying biological pattern formation are difficult to elucidate in most cases due to the overwhelming physiologic complexity associated with the natural context. The understanding of a particular mechanism, not to speak of underlying universal principles, is difficult due to the diversity and uncertainty of the biological systems. Although current genetic and biochemical approaches have greatly advanced our understanding of pattern formation, the progress mainly relies on experimental phenotypes obtained from time- consuming studies of gain or loss of function mutants. It is prevailingly considered that synthetic biology will come to the application age, but more importantly synthetic biology can be used to understand the life. Using periodic stripe pattern formation as a paradigm, we discuss how to apply synthetic biology in understanding biological pattern formation and hereafter foster the applications like tissue engineering.