Wnt signaling plays an important role in embryogenesis and tumorgenesis. Although the mechanism about how Wnts transduce their signaling from receptor frizzled (Fz) to cytosol has not been understood, dishevelled (Dvl...Wnt signaling plays an important role in embryogenesis and tumorgenesis. Although the mechanism about how Wnts transduce their signaling from receptor frizzled (Fz) to cytosol has not been understood, dishevelled (Dvl) protein was considered as the intersection of Wnt signal traffic. In this study, we characterized the function of three domains (DIX,PDZ and DEP) of Dvl-1 in canonical Wnt signal transduction and Dvl-1 membrane translocation. It was found both DIX and DEP domain were sufficient to block Wnt-3a-induced LEF-1 transcriptional activity and free cytosol β-catenin accumulation; whereas PDZ domain and a functional mutant form of DEP domain (DEP-KM) had no effect on canonical Wnt signaling. In addition, when cotransfected with Fz-7, DEP domain, but not DIX, PDZ or DEP-KM, translocated and co-localized with Fz-7 to the plasma membrane, which was similar to Dvl-1. Furthermore, it was DEP domain that could block Fz-7-induced membrane translocation of Dvl- 1 via a possible competitive mechanism. These results strongly suggest that DEP domain is responsible for the membrane translocation of Dvl-1 protein upon Wnt signal stimulation.展开更多
Multinanoparticles interacting with the phospholipid membranes in solution were studied by dissipative particle dynamics simulation.The selected nanoparticles have spherical or cylindrical shapes,and they have various...Multinanoparticles interacting with the phospholipid membranes in solution were studied by dissipative particle dynamics simulation.The selected nanoparticles have spherical or cylindrical shapes,and they have various initial velocities in the dynamical processes.Several translocation modes are defined according to their characteristics in the dynamical processes,in which the phase diagrams are constructed based on the interaction strengths between the particles and membranes and the initial velocities of particles.Furthermore,several parameters,such as the system energy and radius of gyration,are investigated in the dynamical processes for the various translocation modes.Results elucidate the effects of multiparticles interacting with the membranes in the biological processes.展开更多
Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this stud...Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...展开更多
Here we report a family with a clinical spectrum of Pachyonychia Congenita Tarda (PCT) encompassing two generations via a balanced chromosomal translocation between 4q26 and 12p12.3. We discuss the effects of chromoso...Here we report a family with a clinical spectrum of Pachyonychia Congenita Tarda (PCT) encompassing two generations via a balanced chromosomal translocation between 4q26 and 12p12.3. We discuss the effects of chromosomal translocations on gene expression through involved breakpoints and structural gene abnormalities detected by array CGH. We believe that the family we present gives further insight to the better understanding of molecular and structural basis of keratin disorders, and to the late onset and genetic basis of PCT through the possible role of C-type lectins and human epithelial membrane protein1 (EMP1). Better understanding of the molecular basis of keratin disorders is the foundation for improved diagnosis, genetic counseling and novel therapeutic approaches to overcome the current treatment limitations related to this disease.展开更多
Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV encoded proteins, and also it has always been the core of the oncogenic mechanism of EBV. Tradit...Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV encoded proteins, and also it has always been the core of the oncogenic mechanism of EBV. Traditional receptor theory demonstrates that cell surface receptors exert biological functions on the membrane, which neither enter into the nucleus nor directly affect the transcription of the target genes. But, advanced studies on nuclear transloca-tion of the epidermal growth factor receptor (EGFR) family have greatly developed our knowl-edge of the biological function of cell surface receptors. In this study, we used Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1 integrated NPC cell line and the ex-pression of LMP1 in which could be regulated by Tet system. We found that LMP1 could regulate the nuclear translocation of EGFR in a dose-dependent manner from both quantitative and qualitative levels through the Western blot analysis and the immunofluorescent analysis with a laser scanning confocal microscope. We further demonstrated that the nuclear localization se-quence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation, and the nuclear accumulation of EGFR regulated by LMP1 was in a ligand-independent manner. These findings provide a novel view that the regulation of LMP1 on the nuclear translocation of EGFR is critical for the process of nasopharyngeal carcinoma.展开更多
The dependence of import of chicken heart apocytochrome c on its transformation to holoform by heme attachment was studied. Results showed that there was no difference in the translocation of apocytochrome c across th...The dependence of import of chicken heart apocytochrome c on its transformation to holoform by heme attachment was studied. Results showed that there was no difference in the translocation of apocytochrome c across the mitochondrial membrane in the presence or absence of hemin + dithionite. Furthermore, two heme unattached mutants (H18D, C17S) were prepared, which could still be accumulated in mitochondria, but their import velocity was obviously reduced.展开更多
叶绿体作为植物及藻类细胞中含有内外双层被膜的细胞器,能够通过光合作用过程将光能转化为化学能。大部分的叶绿体蛋白由细胞核基因编码,其前体蛋白是在细胞质中的80S核糖体上合成的。前体蛋白在转运肽的引导下,通过跨越叶绿体外被膜和...叶绿体作为植物及藻类细胞中含有内外双层被膜的细胞器,能够通过光合作用过程将光能转化为化学能。大部分的叶绿体蛋白由细胞核基因编码,其前体蛋白是在细胞质中的80S核糖体上合成的。前体蛋白在转运肽的引导下,通过跨越叶绿体外被膜和内被膜的路径被传送进入叶绿体内部,进而到达发挥其生物学功能的目的微区。目前已知的前体蛋白转运的一个主要途径是通过叶绿体外被膜转运子(translocon in the outer envelope membrane of chloroplast, TOC)和内被膜转运子(translocon in the inner envelope membrane of chloroplast, TIC),在二者的协同作用下前体蛋白得以跨越双层被膜进入叶绿体。文章回顾了TOC-TIC超复合物的结构生物学研究进展,并深入探讨了各组件的功能特性以及前体蛋白易位至叶绿体内部的潜在途径和调控机制。展开更多
文摘Wnt signaling plays an important role in embryogenesis and tumorgenesis. Although the mechanism about how Wnts transduce their signaling from receptor frizzled (Fz) to cytosol has not been understood, dishevelled (Dvl) protein was considered as the intersection of Wnt signal traffic. In this study, we characterized the function of three domains (DIX,PDZ and DEP) of Dvl-1 in canonical Wnt signal transduction and Dvl-1 membrane translocation. It was found both DIX and DEP domain were sufficient to block Wnt-3a-induced LEF-1 transcriptional activity and free cytosol β-catenin accumulation; whereas PDZ domain and a functional mutant form of DEP domain (DEP-KM) had no effect on canonical Wnt signaling. In addition, when cotransfected with Fz-7, DEP domain, but not DIX, PDZ or DEP-KM, translocated and co-localized with Fz-7 to the plasma membrane, which was similar to Dvl-1. Furthermore, it was DEP domain that could block Fz-7-induced membrane translocation of Dvl- 1 via a possible competitive mechanism. These results strongly suggest that DEP domain is responsible for the membrane translocation of Dvl-1 protein upon Wnt signal stimulation.
基金the National Natural Science Foundation of China(No.21973070,No.21474076,No.21674082,and No.11875205)。
文摘Multinanoparticles interacting with the phospholipid membranes in solution were studied by dissipative particle dynamics simulation.The selected nanoparticles have spherical or cylindrical shapes,and they have various initial velocities in the dynamical processes.Several translocation modes are defined according to their characteristics in the dynamical processes,in which the phase diagrams are constructed based on the interaction strengths between the particles and membranes and the initial velocities of particles.Furthermore,several parameters,such as the system energy and radius of gyration,are investigated in the dynamical processes for the various translocation modes.Results elucidate the effects of multiparticles interacting with the membranes in the biological processes.
基金This work was supported in part by grants from the National Key Program for Fundamental Research and Development(Grant No.G1999054203)the National Natural Science Outstanding Youth Foundation of China(Grant No.30125020).
文摘Objective:Early multiple organ dysfunction syndrome appears to be facilitated with bacterial transloca-tion in severely burn injury,yet the mechanisms of bacterial translocation remains in dispute.The aim of this studywas to investigate the potential role of intestinal bifidobacteria in the pathogenesis of gut-derived bacteria/endotoxintranslocation following burns and the effects of bifidohacterial supplement on gut barrier.Methods:Wistar rats wererandomly divided into burn group(Burn,n=60),sham burn g...
文摘Here we report a family with a clinical spectrum of Pachyonychia Congenita Tarda (PCT) encompassing two generations via a balanced chromosomal translocation between 4q26 and 12p12.3. We discuss the effects of chromosomal translocations on gene expression through involved breakpoints and structural gene abnormalities detected by array CGH. We believe that the family we present gives further insight to the better understanding of molecular and structural basis of keratin disorders, and to the late onset and genetic basis of PCT through the possible role of C-type lectins and human epithelial membrane protein1 (EMP1). Better understanding of the molecular basis of keratin disorders is the foundation for improved diagnosis, genetic counseling and novel therapeutic approaches to overcome the current treatment limitations related to this disease.
基金This work was supported by the Excellent Young Teachers Program of Ministry of Education of Chian Scientific Developing Program of Beijing Municipal Commission of Education (200KJ080+2 种基金 KM200310025100) Beijing Natural Science Foundation (7032005) Nati
基金This work was supported by the National Natural Science Foundation for Distinguished Young Scholar of China(No.3952502)State Key Basic Research Program,Fundamental Investigation on Human Carcinogenesis of China(No.G1998051201)National Natural Science Foundation of China(Grant No.30300407).
文摘Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV encoded proteins, and also it has always been the core of the oncogenic mechanism of EBV. Traditional receptor theory demonstrates that cell surface receptors exert biological functions on the membrane, which neither enter into the nucleus nor directly affect the transcription of the target genes. But, advanced studies on nuclear transloca-tion of the epidermal growth factor receptor (EGFR) family have greatly developed our knowl-edge of the biological function of cell surface receptors. In this study, we used Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1 integrated NPC cell line and the ex-pression of LMP1 in which could be regulated by Tet system. We found that LMP1 could regulate the nuclear translocation of EGFR in a dose-dependent manner from both quantitative and qualitative levels through the Western blot analysis and the immunofluorescent analysis with a laser scanning confocal microscope. We further demonstrated that the nuclear localization se-quence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation, and the nuclear accumulation of EGFR regulated by LMP1 was in a ligand-independent manner. These findings provide a novel view that the regulation of LMP1 on the nuclear translocation of EGFR is critical for the process of nasopharyngeal carcinoma.
基金Project supported by the National Natural Science Foundation of China (Grant No. 39730130).
文摘The dependence of import of chicken heart apocytochrome c on its transformation to holoform by heme attachment was studied. Results showed that there was no difference in the translocation of apocytochrome c across the mitochondrial membrane in the presence or absence of hemin + dithionite. Furthermore, two heme unattached mutants (H18D, C17S) were prepared, which could still be accumulated in mitochondria, but their import velocity was obviously reduced.
文摘叶绿体作为植物及藻类细胞中含有内外双层被膜的细胞器,能够通过光合作用过程将光能转化为化学能。大部分的叶绿体蛋白由细胞核基因编码,其前体蛋白是在细胞质中的80S核糖体上合成的。前体蛋白在转运肽的引导下,通过跨越叶绿体外被膜和内被膜的路径被传送进入叶绿体内部,进而到达发挥其生物学功能的目的微区。目前已知的前体蛋白转运的一个主要途径是通过叶绿体外被膜转运子(translocon in the outer envelope membrane of chloroplast, TOC)和内被膜转运子(translocon in the inner envelope membrane of chloroplast, TIC),在二者的协同作用下前体蛋白得以跨越双层被膜进入叶绿体。文章回顾了TOC-TIC超复合物的结构生物学研究进展,并深入探讨了各组件的功能特性以及前体蛋白易位至叶绿体内部的潜在途径和调控机制。
