Showing papers by "Osaka University published in 1998"
TL;DR: Sequencing of c-kit complementary DNA from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains, suggesting that the mutations contribute to tumor development.
Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutively activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34.
4,311 citations
University of Tokyo1, Boston University2, Brookhaven National Laboratory3, University of California, Irvine4, California State University5, George Mason University6, Gifu University7, University of Hawaii at Manoa8, Kobe University9, Los Alamos National Laboratory10, Louisiana State University11, University of Maryland, College Park12, University of Chicago13, Stony Brook University14, Niigata University15, Osaka University16, Seoul National University17, Tohoku University18, Tokai University19, Tokyo Institute of Technology20, University of Warsaw21, University of Washington22, Stanford University23
Abstract: We present an analysis of atmospheric neutrino data from a 33.0 kton yr (535-day) exposure of the Super-Kamiokande detector. The data exhibit a zenith angle dependent deficit of muon neutrinos which is inconsistent with expectations based on calculations of the atmospheric neutrino flux. Experimental biases and uncertainties in the prediction of neutrino fluxes and cross sections are unable to explain our observation. The data are consistent, however, with two-flavor ${\ensuremath{
u}}_{\ensuremath{\mu}}\ensuremath{\leftrightarrow}{\ensuremath{
u}}_{\ensuremath{\tau}}$ oscillations with ${sin}^{2}2\ensuremath{\theta}g0.82$ and $5\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}4}l\ensuremath{\Delta}{m}^{2}l6\ifmmode\times\else\texttimes\fi{}1{0}^{\ensuremath{-}3}\mathrm{eV}{}^{2}$ at 90% confidence level.
3,784 citations
TL;DR: A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells and seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity.
Abstract: The homeostasis of animals is regulated not only by the growth and differentiation of cells, but also by cell death through a process known as apoptosis. Apoptosis is mediated by members of the caspase family of proteases, and eventually causes the degradation of chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long and a short form. Recombinant ICAD specifically inhibits CAD-induced degradation of nuclear DNA and its DNase activity. When CAD is expressed with ICAD in COS cells or in a cell-free system, CAD is produced as a complex with ICAD: treatment with caspase 3 releases the DNase activity which causes DNA fragmentation in nuclei. ICAD therefore seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity; caspases activated by apoptotic stimuli then cleave ICAD, allowing CAD to enter the nucleus and degrade chromosomal DNA.
3,248 citations
2,804 citations
TL;DR: To explore the role of cyclooxygenase (COX) in endothelial cell migration and angiogenesis, two in vitro model systems involving coculture of endothelial cells with colon carcinoma cells are used.
2,263 citations
TL;DR: It is found that mice deficient for CXCR4 die perinatally and display profound defects in the hematopoietic and nervous systems, and Identical defects are observed in mice lacking SDF-1, suggesting a monogamous relationship between CX CR4 and S DF-1.
Abstract: The chemokine stromal cell-derived factor 1, SDF-1, is an important regulator of leukocyte and hematopoietic precursor migration and pre-B cell proliferation. The receptor for SDF-1, CXCR4, also functions as a coreceptor for T-tropic HIV-1 entry. We find that mice deficient for CXCR4 die perinatally and display profound defects in the hematopoietic and nervous systems. CXCR4-deficient mice have severely reduced B-lymphopoiesis, reduced myelopoiesis in fetal liver, and a virtual absence of myelopoiesis in bone marrow. However, T-lymphopoiesis is unaffected. Furthermore, the cerebellum develops abnormally with an irregular external granule cell layer, ectopically located Purkinje cells, and numerous chromophilic cell clumps of abnormally migrated granule cells within the cerebellar anlage. Identical defects are observed in mice lacking SDF-1, suggesting a monogamous relationship between CXCR4 and SDF-1. This receptor-ligand selectivity is unusual among chemokines and their receptors, as is the function in migration of nonhematopoietic cells.
1,694 citations
TL;DR: The results indicate that activation of CAD downstream of the caspase cascade is responsible for internucleosomal DNA degradation during apoptosis, and that ICAD works as an inhibitor of this process.
Abstract: Various molecules such as cytokines and anticancer drugs, as well as factor deprivation, rapidly induce apoptosis (programmed cell death), which is morphologically characterized by cell shrinkage and the blebbing of plasma membranes and by nuclear condensation. Caspases, particularly caspase 3, are proteases that are activated during apoptosis and which cleave substrates such as poly(ADP-ribose) polymerase, actin, fodrin, and lamin. Apoptosis is also accompanied by the internucleosomal degradation of chromosomal DNA. In the accompanying Article, we have identified and molecularly cloned a caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD). Here we show that caspase 3 cleaves ICAD and inactivates its CAD-inhibitory effect. We identified two caspase-3 cleavage sites in ICAD by site-directed mutagenesis. When human Jurkat cells were transformed with ICAD-expressing plasmid, occupation of the receptor Fas, which normally triggers apoptosis, did not result in DNA degradation. The ICAD transformants were also resistant to staurosporine-induced DNA degradation, although staurosporine still killed the cells by activating caspase. Our results indicate that activation of CAD downstream of the caspase cascade is responsible for internucleosomal DNA degradation during apoptosis, and that ICAD works as an inhibitor of this process.
1,612 citations
TL;DR: PBSF/SDF-1 and CXCR4 define a new signalling system for organ vascularization, and it is reported that CX CR4 is expressed in developing vascular endothelial cells, and that mice lacking CxCR4 or PBSF/ sdf-1 have defective formation of the large vessels supplying the gastrointestinal tract.
Abstract: Vascularization of organs generally occurs by remodelling of the preexisting vascular system during their differentiation and growth to enable them to perform their specific functions during development. The molecules required by early vascular systems, many of which are receptor tyrosine kinases and their ligands, have been defined by analysis of mutant mice. As most of these mice die during early gestation before many of their organs have developed, the molecules responsible for vascularization during organogenesis have not been identified. The cell-surface receptor CXCR4 is a seven-transmembrane-spanning, G-protein-coupled receptor for the CXC chemokine PBSF/SDF-1 (for pre-B-cell growth-stimulating factor/stromal-cell-derived factor), which is responsible for B-cell lymphopoiesis, bone-marrow myelopoiesis and cardiac ventricular septum formation. CXCR4 also functions as a co-receptor for T-cell-line tropic human immunodeficiency virus HIV-1. Here we report that CXCR4 is expressed in developing vascular endothelial cells, and that mice lacking CXCR4 or PBSF/SDF-1 have defective formation of the large vessels supplying the gastrointestinal tract. In addition, mice lacking CXCR4 die in utero and are defective in vascular development, haematopoiesis and cardiogenesis, like mice lacking PBSF/SDF-1, indicating that CXCR4 is a primary physiological receptor for PBSF/SDF-1. We conclude that PBSF/SDF-1 and CXCR4 define a new signalling system for organ vascularization.
1,553 citations
TL;DR: It is suggested that acidification of the lumenal space of autophagosomes or lysosomes by V-ATPase is important for the fusion between autophagic vacuoles and lyssosomes.
Abstract: We studied the effects of bafilomycin A1, a potent and specific inhibitor of vacuolar H+ ATPase (V-ATPase), on the process of autophagy in rat hepatoma cell line, H-4-II-E cells. To induce autophagy, cells were transferred from Dulbecco's modified Eagle medium containing 12% fetal calf serum into Hanks' balanced salt solution. When bafilomycin A1 was added to Hanks' balanced salt solution, endogenous protein degradation was strongly inhibited and numerous autophagosomes accumulated in H-4-II-E cells, whereas autolysosomes decreased in number. Acid phosphatase activity was not detected in the autophagosomes which accumulated in the presence of bafilomycin A1, suggesting that fusion between autophagosomes and lysosomes was disturbed by this drug. Inhibition of the fusion was reversible, and the autophagosomes changed into autolysosomes after the removal of the inhibitor. Bafilomycin A1 also prevented the appearance of endocytosed HRP in autophagic vacuoles. These results suggested that acidification of the lumenal space of autophagosomes or lysosomes by V-ATPase is important for the fusion between autophagosomes and lysosomes.
1,281 citations
TL;DR: Observations provide the first genetic evidence that both repair pathways play a role in maintaining chromosomal DNA during the cell cycle.
Abstract: Eukaryotic cells repair DNA double-strand breaks (DSBs) by at least two pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ). Rad54 participates in the first recombinational repair pathway while Ku proteins are involved in NHEJ. To investigate the distinctive as well as redundant roles of these two repair pathways, we analyzed the mutants RAD54(-/-), KU70(-/-) and RAD54(-/-)/KU70(-/-), generated from the chicken B-cell line DT40. We found that the NHEJ pathway plays a dominant role in repairing gamma-radiation-induced DSBs during G1-early S phase while recombinational repair is preferentially used in late S-G2 phase. RAD54(-/-)/KU70(-/-) cells were profoundly more sensitive to gamma-rays than either single mutant, indicating that the two repair pathways are complementary. Spontaneous chromosomal aberrations and cell death were observed in both RAD54(-/-) and RAD54(-/-)/KU70(-/-) cells, with RAD54(-/-)/KU70(-/-) cells exhibiting significantly higher levels of chromosomal aberrations than RAD54(-/-) cells. These observations provide the first genetic evidence that both repair pathways play a role in maintaining chromosomal DNA during the cell cycle.
1,275 citations
TL;DR: In this article, the authors studied the defect physics in a chalcopyrite semiconductor and showed that it takes much less energy to form a Cu vacancy in the semiconductor than to form cation vacancies in II-VI compounds and that defect formation energies vary considerably both with the Fermi energy and with the chemical potential of the atomic species.
Abstract: We studied the defect physics in ${\mathrm{CuInSe}}_{2},$ a prototype chalcopyrite semiconductor. We showed that (i) it takes much less energy to form a Cu vacancy in ${\mathrm{CuInSe}}_{2}$ than to form cation vacancies in II-VI compounds (ii) defect formation energies vary considerably both with the Fermi energy and with the chemical potential of the atomic species, and (iii) the defect pairs such as $({2\mathrm{V}}_{\mathrm{Cu}}^{\mathrm{\ensuremath{-}}}{+\mathrm{I}\mathrm{n}}_{\mathrm{Cu}}^{2+})$ and $({2\mathrm{C}\mathrm{u}}_{\mathrm{In}}^{2\mathrm{\ensuremath{-}}}{+\mathrm{I}\mathrm{n}}_{\mathrm{Cu}}^{2+})$ have particularly low formation energies (under certain conditions, even exothermic). Using (i)--(iii), we (a) explain the existence of unusual ordered compounds ${\mathrm{CuIn}}_{5}{\mathrm{Se}}_{8},$ ${\mathrm{CuIn}}_{3}{\mathrm{Se}}_{5},$ ${\mathrm{Cu}}_{2}{\mathrm{In}}_{4}{\mathrm{Se}}_{7},$ and ${\mathrm{Cu}}_{3}{\mathrm{In}}_{5}{\mathrm{Se}}_{9}$ as a repeat of a single unit of $({2\mathrm{V}}_{\mathrm{Cu}}^{\mathrm{\ensuremath{-}}}{+\mathrm{I}\mathrm{n}}_{\mathrm{Cu}}^{2+})$ pairs for each $n=4,$ 5, 7, and 9 units, respectively, of ${\mathrm{CuInSe}}_{2};$ (b) attribute the very efficient $p$-type self-doping ability of ${\mathrm{CuInSe}}_{2}$ to the exceptionally low formation energy of the shallow defect Cu vacancies; (c) explained in terms of an electronic passivation of the ${\mathrm{In}}_{\mathrm{Cu}}^{2+}$ by ${2\mathrm{V}}_{\mathrm{Cu}}^{\mathrm{\ensuremath{-}}}$ the electrically benign character of the large defect population in ${\mathrm{CuInSe}}_{2}.$ Our calculation leads to a set of new assignment of the observed defect transition energy levels in the band gap. The calculated level positions agree rather well with available experimental data.
TL;DR: The usefulness of the method is demonstrated by the segmentation and visualization of brain vessels from magnetic resonance imaging and magnetic resonance angiography, bronchi from a chest CT, and liver vessels (portal veins) from an abdominal CT.
TL;DR: It is suggested that proapoptotic Bcl-2 family proteins, including Bax and Bak, induce the mitochondrial PT and cytochrome c release by interacting with the PT pores.
Abstract: Cytochrome c release and the mitochondrial permeability transition (PT), including loss of the transmembrane potential (Δψ), play an important role in apoptosis. Using isolated mitochondria, we found that recombinant Bax and Bak, proapoptotic members of the Bcl-2 family, induced mitochondrial Δψ loss, swelling, and cytochrome c release. All of these changes were dependent on Ca2+ and were prevented by cyclosporin A (CsA) and bongkrekic acid, both of which close the PT pores (megachannels), indicating that Bax- and Bak-induced mitochondrial changes were mediated through the opening of these pores. Bax-induced mitochondrial changes were inhibited by recombinant Bcl-xL and transgene-derived Bcl-2, antiapoptotic members of the Bcl-2 family, as well as by oligomycin, suggesting a possible regulatory effect of F0F1-ATPase on Bax-induced mitochondrial changes. Proapoptotic Bax- and Bak-BH3 (Bcl-2 homology) peptides, but not a mutant BH3 peptide nor a mutant Bak lacking BH3, induced the mitochondrial changes, indicating an essential role of the BH3 region. A coimmunoprecipitation study revealed that Bax and Bak interacted with the voltage-dependent anion channel, which is a component of PT pores. Taken together, these findings suggest that proapoptotic Bcl-2 family proteins, including Bax and Bak, induce the mitochondrial PT and cytochrome c release by interacting with the PT pores.
TL;DR: In this article, the applicability of in vivo electroporation for gene transfer into muscle, using plasmid DNA expressing interleukin-5 (IL-5) as the vector, was investigated.
Abstract: Among the nonviral techniques for gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple, inexpensive, and safe. Applications of this method have been limited by the relatively low expression levels of the transferred gene. We investigated the applicability of in vivo electroporation for gene transfer into muscle, using plasmid DNA expressing interleukin-5 (IL-5) as the vector. The tibialis anterior muscles of mice were injected with the plasmid DNA, and then a pair of electrode needles were inserted into the DNA injection site to deliver electric pulses. Five days later, the serum IL-5 levels were assayed. Mice that did not receive electroporation had serum levels of 0.2 ng/ml. Electroporation enhanced the levels to over 20 ng/ml. Histochemical analysis of muscles injected with a lacZ expression plasmid showed that in vivo electroporation increased both the number of muscle fibers taking up plasmid DNA and the copy number of plasmids introduced into the cells. These results demonstrate that gene transfer into muscle by electroporation in vivo is more efficient than simple intramuscular DNA injection.
TL;DR: The in vivo role of IL-18 and IL-12 in NK activity, as well as in in vivo Th1 response is demonstrated, demonstrating the important role of both IL- 18 andIL-12 as cytokine secreted from activated macrophages and induces IFNgamma production.
TL;DR: A novel DNA damage recognition-competition assay is used to identify XPC-HR23B as the earliest damage detector to initiate NER: it acts before the known damage-binding protein XPA, providing a plausible explanation for the extreme damage specificity exhibited by global genome repair.
TL;DR: Evidence is shown that LMB binds directly to CRM1 and thatCRM1 is essential for NES-dependent nuclear export of proteins in both yeast and mammalian cells, and is an essential factor for nuclear exported proteins in eukaryotes.
TL;DR: In this article, the relativistic mean field (RMF) theory was used to construct the EOS of homogeneous nuclear matter, where heavy nuclei are formed together with free nucleon gas.
TL;DR: In this paper, the authors used 17O NMR to determine the spin susceptibility of the layered oxide superconductor Sr2RuO4 and showed no change in spin susceptibility on passing through the superconducting transition temperature.
Abstract: Superconductivity — one of the best understood many-body problems in physics — has again become a challenge following the discovery of unconventional superconducting materials: these include heavy-fermion1, organic2 and the high-transition-temperature copper oxide3 superconductors In conventional superconductors, the electrons form superconducting Cooper pairs in a spin-singlet state, which has zero total spin (S = 0) In principle, Cooper pairs can also form in a spin-triplet state (S = 1), analogous to the spin-triplet ‘p-wave’ state of paired neutral fermions in superfluid 3He (ref 4) At present, the heavy-fermion compound UPt3 is the only known spin-triplet superconductor5,6, although the layered oxide superconductor Sr2RuO4 (ref 7) is believed, on theoretical grounds8, to be a promising candidate The most direct means of identifying the spin state of Cooper pairs is from measurements of their spin susceptibility, which can be determined by the Knight shift (as probed by nuclear magnetic resonance (NMR)) Here we report Knight-shift measurements of Sr2RuO2 using 17O NMR Our results show no change in spin susceptibility on passing through the superconducting transition temperature, which provides the definitive identification of Sr2RuO4 as a spin-triplet superconductor
TL;DR: JAK tyrosine kinase is a key molecule that can initiate multiple signal-transduction pathways by inducing the tyrosinesine-phosphorylation of the cytokine receptor, gp130 in the case of IL-6, on which several signaling molecules are recruited, including STAT, a signal transducer and activator of transcription, and SHP-2, which links to the Ras-MAP kinase pathway.
Abstract: Ten years have passed since the molecular cloning of interleukin 6 (IL-6) in 1986. IL-6 is a typical cytokine, exhibiting functional pleiotropy and redundancy. IL-6 is involved in the immune response, inflammation, and hematopoiesis. The IL-6 receptor consists of an IL-6 binding alpha chain and a signal transducer, gp130, which is shared among the receptors for the IL-6 related cytokine subfamily. The sharing of a receptor subunit is a general feature of cytokine receptors and provides the molecular basis for the functional redundancy of cytokines. JAK tyrosine kinase is a key molecule that can initiate multiple signal-transduction pathways by inducing the tyrosine-phosphorylation of the cytokine receptor, gp130 in the case of IL-6, on which several signaling molecules are recruited, including STAT, a signal transducer and activator of transcription, and SHP-2, which links to the Ras-MAP kinase pathway. JAK can also directly activate signaling molecules such as STAT and Tec. These multiple signal-transduction pathways intimately regulate the expression of several genes including c-myc, c-myb, junB, IRF1, egr-1, and bcl-2, leading to the induction of cell growth, differentiation, and survival. The deregulated expression of IL-6 and its receptor is involved in a variety of diseases.
TL;DR: It is found that pro-caspase-11 physically interacts with pro-ICE in cells, and the expression of casp-11 is essential for activation of ICE.
TL;DR: Results indicate that the membrane-bound form of FasL is the functional form and suggest that shedding of Fas L is to prevent the killing of the healthy bystander cells by cytotoxic T cells.
Abstract: Apoptosis-inducing Fas ligand (FasL) is a type II membrane protein, predominantly expressed in the activated T cells. FasL is cleaved by a putative metalloproteinase to produce a soluble form. Here, we blocked the shedding of human FasL by deleting its cleavage site. Although human Jurkat cells and mouse primary hepatocytes that express a low level of Fas were resistant to the soluble form of FasL, they were efficiently killed by membrane-bound FasL. Furthermore, soluble FasL inhibited cytotoxicity of the membrane-bound FasL. These results indicate that the membrane-bound form of FasL is the functional form and suggest that shedding of FasL is to prevent the killing of the healthy bystander cells by cytotoxic T cells.
TL;DR: In this article, the carrier-induced ferromagnetism in doped diluted magnetic semiconductors was investigated using the Korringa-Kohn-Rostoker coherent-potential approximation and local density approximation first-principles calculation.
Abstract: Carrier-induced ferromagnetism in the doped diluted magnetic semiconductors $(\mathrm{In},\mathrm{Mn}\ensuremath{\uparrow},\mathrm{Mn}\ensuremath{\downarrow},A)\mathrm{As}$, where $A$ is As or Sn and $\mathrm{Mn}\ensuremath{\uparrow}$ ( $\mathrm{Mn}\ensuremath{\downarrow}$) denotes Mn atoms whose local magnetic moment is parallel (antiparallel) to the magnetization, are investigated using the Korringa-Kohn-Rostoker coherent-potential approximation and local density approximation first-principles calculation The result shows that (i) the ferromagnetic state is stable due to the double exchange at low concentrations of $A$, and (ii) a spin-glass-like local-moment disordered state, which stems from the superexchange, is more favorable when the Mn $d$ holes are nearly compensated
TL;DR: It is demonstrated that before it can induce filopodium formation, Cdc42 must bind a WASP-related protein, N-WASP, that is richest in neural tissues but is expressed ubiquitously.
Abstract: Cdc42 is a small GTPase of the Rho family which regulates the formation of actin filaments to generate filopodia1,2. Although there are several proteins such as PAK3, ACK4 and WASP (Wiskott–Aldrich syndrome protein)5 that bind Cdc42 directly, none of these can account for the filopodium formation induced by Cdc42. Here we demonstrate that before it can induce filopodium formation, Cdc42 must bind a WASP-related protein, N-WASP, that is richest in neural tissues6 but is expressed ubiquitously. N-WASP induces extremely long actin microspikes only when co-expressed with active Cdc42, whereas WASP, which is expressed in haematopoietic cells, does not, despite the structural similarities between WASP and N-WASP. In a cell-free system, addition of active Cdc42 significantly stimulates the actin-depolymerizing activity of N-WASP, creating free barbed ends from which actin polymerization can then take place. This activation seems to be caused by exposure of N-WASP's actin-depolymerizing region induced by Cdc42 binding.
University of Tokyo1, Boston University2, Seoul National University3, Brookhaven National Laboratory4, University of California, Irvine5, California State University6, George Mason University7, Gifu University8, University of Hawaii at Manoa9, Kobe University10, Los Alamos National Laboratory11, Louisiana State University12, University of Maryland, College Park13, University of Chicago14, Miyagi University of Education15, Stony Brook University16, Niigata University17, Shizuoka University18, Osaka University19, Tohoku University20, Tokai University21, Tokyo Institute of Technology22, University of Warsaw23, University of Washington24
TL;DR: The first results of the solar neutrino flux measurement from Super-Kamiokande are presented in this article, where the results are obtained from data taken between 31 May 1996, and 23 June 1997.
Abstract: The first results of the solar neutrino flux measurement from Super-Kamiokande are presented. The results shown here are obtained from data taken between 31 May 1996, and 23 June 1997. Using our measurement of recoil electrons with energies above 6.5 MeV, we infer the total flux of ${}^{8}\mathrm{B}$ solar neutrinos to be $2.42\ifmmode\pm\else\textpm\fi{}0.06(\mathrm{stat}{)}_{\ensuremath{-}0.07}^{+0.10}(\mathrm{syst})\ifmmode\times\else\texttimes\fi{}{10}^{6}\mathrm{cm}{}^{\ensuremath{-}2}{\mathrm{s}}^{\ensuremath{-}1}$. This result is consistent with the Kamiokande measurement and is 36% of the flux predicted by the BP95 solar model. The flux is also measured in 1.5 month subsets and shown to be consistent with a constant rate.
TL;DR: The Bcl‐2 family of proteins acts as a critical life–death decision point within the common pathway of apoptosis, whereby members of this family trigger the release of caspases from death antagonists via heterodimerization and also by inducing therelease of mitochondrial apoptogenic factors into the cytoplasm via acting on mitochondrial permeability transition pore.
Abstract: Apoptosis is an essential physiological process for the selective elimination of cells, which is involved in a variety of biological events. The Bcl-2 family is the best characterized protein family involved in the regulation of apoptotic cell death, consisting of anti-apoptotic and pro-apoptotic members. The anti-apoptotic members of this family, such as Bcl-2 and Bcl-XL, prevent apoptosis either by sequestering proforms of death-driving cysteine proteases called caspases (a complex called the apoptosome) or by preventing the release of mitochondrial apoptogenic factors such as cytochrome c and AIF (apoptosis-inducing factor) into the cytoplasm. After entering the cytoplasm, cytochrome c and AIF directly activate caspases that cleave a set of cellular proteins to cause apoptotic changes. In contrast, pro-apoptotic members of this family, such as Bax and Bak, trigger the release of caspases from death antagonists via heterodimerization and also by inducing the release of mitochondrial apoptogenic factors into the cytoplasm via acting on mitochondrial permeability transition pore, thereby leading to caspase activation. Thus, the Bcl-2 family of proteins acts as a critical life-death decision point within the common pathway of apoptosis.
TL;DR: Bicyclic nucleoside analogues with a fixed N-type conformation, 2′-O,4′-C-methyleneuridine and -cytidine, were incorporated into oligonucleotides, and the binding efficiency of the modified oligon nucleotides to the complementary DNA and RNA as well as the CD spectra of themodified DNA-DNA and modified DNA-RNA duplexes were studied.