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71.
LKB1 modulates lung cancer differentiation and metastasis 总被引:1,自引:0,他引:1
Ji H Ramsey MR Hayes DN Fan C McNamara K Kozlowski P Torrice C Wu MC Shimamura T Perera SA Liang MC Cai D Naumov GN Bao L Contreras CM Li D Chen L Krishnamurthy J Koivunen J Chirieac LR Padera RF Bronson RT Lindeman NI Christiani DC Lin X Shapiro GI Jänne PA Johnson BE Meyerson M Kwiatkowski DJ Castrillon DH Bardeesy N Sharpless NE Wong KK 《Nature》2007,448(7155):807-810
Germline mutation in serine/threonine kinase 11 (STK11, also called LKB1) results in Peutz-Jeghers syndrome, characterized by intestinal hamartomas and increased incidence of epithelial cancers. Although uncommon in most sporadic cancers, inactivating somatic mutations of LKB1 have been reported in primary human lung adenocarcinomas and derivative cell lines. Here we used a somatically activatable mutant Kras-driven model of mouse lung cancer to compare the role of Lkb1 to other tumour suppressors in lung cancer. Although Kras mutation cooperated with loss of p53 or Ink4a/Arf (also known as Cdkn2a) in this system, the strongest cooperation was seen with homozygous inactivation of Lkb1. Lkb1-deficient tumours demonstrated shorter latency, an expanded histological spectrum (adeno-, squamous and large-cell carcinoma) and more frequent metastasis compared to tumours lacking p53 or Ink4a/Arf. Pulmonary tumorigenesis was also accelerated by hemizygous inactivation of Lkb1. Consistent with these findings, inactivation of LKB1 was found in 34% and 19% of 144 analysed human lung adenocarcinomas and squamous cell carcinomas, respectively. Expression profiling in human lung cancer cell lines and mouse lung tumours identified a variety of metastasis-promoting genes, such as NEDD9, VEGFC and CD24, as targets of LKB1 repression in lung cancer. These studies establish LKB1 as a critical barrier to pulmonary tumorigenesis, controlling initiation, differentiation and metastasis. 相似文献
72.
Douglas JF Iwasawa H Sun Z Fedorov AV Ishikado M Saitoh T Eisaki H Bando H Iwase T Ino A Arita M Shimada K Namatame H Taniguchi M Masui T Tajima S Fujita K Uchida S Aiura Y Dessau DS 《Nature》2007,446(7133):E5
The possibility that a pairing boson might act as the 'glue' to bind electrons into a Cooper pair in superconductors with a high critical temperature (T(c)) is being actively pursued in condensed-matter physics. Gweon et al. claim that there is a large and unusual oxygen-isotope effect on the electronic structure, indicating that phonons have a special importance in high-temperature superconductors. However, we are unable to detect this unusual oxygen-isotope effect in new data collected under almost identical material and experimental conditions. Our findings point towards a more conventional influence of phonons in these materials. 相似文献
73.
Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However,
it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation induces selective
autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing
of the ubiquitin-editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by
an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes,
including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting ‘autophagy receptors’
in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52
was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly,
only under the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)-induced proinflammatory gene expression.
Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF–TRAF6. Furthermore,
although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning
effect of NDP52 on TLR signaling. 相似文献
74.
Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture. 总被引:21,自引:0,他引:21
Y Matsui D Toksoz S Nishikawa S Nishikawa D Williams K Zsebo B L Hogan 《Nature》1991,353(6346):750-752
Despite the importance of germ cells to the survival of species, surprisingly little is known about their embryological origin, proliferation, migration and entry into mitotic arrest or meiosis. Mutations in the murine Dominant White Spotting (W) and Steel genes, which respectively encode the c-kit tyrosine kinase receptor and the c-kit ligand (or Steel factor), impair the development of primordial germ cells (PGCs) in vivo, as well as haematopoietic stem cells and neural crest-derived melanoblasts. Here we use a monoclonal antibody against c-kit tyrosine kinase receptor and recombinant Steel factor to study the c-kit receptor-ligand system in cultured PGCs. In addition, we show that leukaemia inhibitory factor (also known as differentiation inhibitory activity), a factor secreted by STO fibroblasts, can stimulate proliferation of primordial germ cells in vitro. 相似文献
75.
最近, 用高温超导单晶Bi2Sr2CaCu2O8+x 制备本征结器件从而实现太赫兹辐射源的研究有较大突破, 而本征结器件的样品制作仍需细致而深入的研究. 为此我们首先借助于单晶硅, 制作了矩形的高台(mesa)结构, 观测了在不同离子加速电压和不同离子束入射角度下, 氩离子铣的刻蚀速度和刻蚀形成台阶侧壁的形貌, 给出了一种刻蚀速率高、台阶侧壁陡峭、对样品损伤小的刻蚀方案, 用此方法加工出的高温超导本征结器件在一定条件下可以得到太赫兹辐射信号. 相似文献
76.
Takeshi Ohkuma 《复旦学报(自然科学版)》2005,44(5)
1Introduction
Asymmetric hydrogenation of ketones is one of the most reliable methods for obtaining chiral secondary alcohols. This transformation is not only of academic interest, but also of industrial significance because of its simplicity, environmental friendliness, and economic viability. Chiral RuXY(binap)(1,2-diamine) complexes (BINAP = 2,2'-bis(diphenyl-phosphino)-1, 1'-binaphthyl,X = Y = C1 or X = H, Y = BH4) with[1] or without[2] a strong base catalyze rapid, highly productive asymmetric hydrogenation of various simple ketones in 2-propanol. This reaction, unlike conventional hydrogenation, proceeds selectively at a C = O bond leaving coexisting C = C linkages intact. A range of chiral alcohols are accessible in high enantiomeric purity from aromatic,heteroaromatic, olefinic, and amino ketones by this method[1,2]. However, no universal chiral catalysts exist due to the structural diversity of ketonic substrates. Thus, tert-alkyl ketones and 1-tetralones have remained difficult to be hydrogenated with high reactivity and enantioselectivity. We here report that this problem can be resolved by the use of BINAP/PICA-Ru (PICA = α-picolylamine)[3] or BINAP/1,4-diamine-Ru[4] complexes as catalysts. 相似文献
77.
Takeshi Ohkuma 《复旦学报(自然科学版)》2005,44(5):762-763
Asymmetric hydrogenation of ketones is one of the most reliable methods for obtaining chiral secondary alcohols. This transformation is not only of academic interest, but also of industrial significance because of its simplicity, environmental friendliness, and economic viability. Chiral RuXY(binap)(1,2-diamine) complexes (BINAP= 2,2'-bis(diphenyl-phosphino)-1, 1'-binaphthyl,X = Y = C1 or X = H, Y = BH4) with or without a strong base catalyze rapid, highly productive asymmetric hydrogenation of various simple ketones in 2-propanol. This reaction, unlike conventional hydrogenation, 相似文献
78.
In viruses, as in eukaryotes, elaborate mechanisms have evolved to protect the genome and to ensure its timely replication and reliable transmission to progeny. Influenza A viruses are enveloped, spherical or filamentous structures, ranging from 80 to 120 nm in diameter. Inside each envelope is a viral genome consisting of eight single-stranded negative-sense RNA segments of 890 to 2,341 nucleotides each. These segments are associated with nucleoprotein and three polymerase subunits, designated PA, PB1 and PB2; the resultant ribonucleoprotein complexes (RNPs) resemble a twisted rod (10-15 nm in width and 30-120 nm in length) that is folded back and coiled on itself. Late in viral infection, newly synthesized RNPs are transported from the nucleus to the plasma membrane, where they are incorporated into progeny virions capable of infecting other cells. Here we show, by transmission electron microscopy of serially sectioned virions, that the RNPs of influenza A virus are organized in a distinct pattern (seven segments of different lengths surrounding a central segment). The individual RNPs are suspended from the interior of the viral envelope at the distal end of the budding virion and are oriented perpendicular to the budding tip. This finding argues against random incorporation of RNPs into virions, supporting instead a model in which each segment contains specific incorporation signals that enable the RNPs to be recruited and packaged as a complete set. A selective mechanism of RNP incorporation into virions and the unique organization of the eight RNP segments may be crucial to maintaining the integrity of the viral genome during repeated cycles of replication. 相似文献
79.
Sub1A is an ethylene-response-factor-like gene that confers submergence tolerance to rice 总被引:10,自引:0,他引:10
Xu K Xu X Fukao T Canlas P Maghirang-Rodriguez R Heuer S Ismail AM Bailey-Serres J Ronald PC Mackill DJ 《Nature》2006,442(7103):705-708
Most Oryza sativa cultivars die within a week of complete submergence--a major constraint to rice production in south and southeast Asia that causes annual losses of over US 1 billion dollars and affects disproportionately the poorest farmers in the world. A few cultivars, such as the O. sativa ssp. indica cultivar FR13A, are highly tolerant and survive up to two weeks of complete submergence owing to a major quantitative trait locus designated Submergence 1 (Sub1) near the centromere of chromosome 9 (refs 3, 4, 5-6). Here we describe the identification of a cluster of three genes at the Sub1 locus, encoding putative ethylene response factors. Two of these genes, Sub1B and Sub1C, are invariably present in the Sub1 region of all rice accessions analysed. In contrast, the presence of Sub1A is variable. A survey identified two alleles within those indica varieties that possess this gene: a tolerance-specific allele named Sub1A-1 and an intolerance-specific allele named Sub1A-2. Overexpression of Sub1A-1 in a submergence-intolerant O. sativa ssp. japonica conferred enhanced tolerance to the plants, downregulation of Sub1C and upregulation of Alcohol dehydrogenase 1 (Adh1), indicating that Sub1A-1 is a primary determinant of submergence tolerance. The FR13A Sub1 locus was introgressed into a widely grown Asian rice cultivar using marker-assisted selection. The new variety maintains the high yield and other agronomic properties of the recurrent parent and is tolerant to submergence. Cultivation of this variety is expected to provide protection against damaging floods and increase crop security for farmers. 相似文献
80.