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排序方式: 共有490条查询结果,搜索用时 15 毫秒
81.
Androutsellis-Theotokis A Leker RR Soldner F Hoeppner DJ Ravin R Poser SW Rueger MA Bae SK Kittappa R McKay RD 《Nature》2006,442(7104):823-826
82.
83.
Gandin V Miluzio A Barbieri AM Beugnet A Kiyokawa H Marchisio PC Biffo S 《Nature》2008,455(7213):684-688
Cell growth and proliferation require coordinated ribosomal biogenesis and translation. Eukaryotic initiation factors (eIFs) control translation at the rate-limiting step of initiation. So far, only two eIFs connect extracellular stimuli to global translation rates: eIF4E acts in the eIF4F complex and regulates binding of capped messenger RNA to 40S subunits, downstream of growth factors, and eIF2 controls loading of the ternary complex on the 40S subunit and is inhibited on stress stimuli. No eIFs have been found to link extracellular stimuli to the activity of the large 60S ribosomal subunit. eIF6 binds 60S ribosomes precluding ribosome joining in vitro. However, studies in yeasts showed that eIF6 is required for ribosome biogenesis rather than translation. Here we show that mammalian eIF6 is required for efficient initiation of translation, in vivo. eIF6 null embryos are lethal at preimplantation. Heterozygous mice have 50% reduction of eIF6 levels in all tissues, and show reduced mass of hepatic and adipose tissues due to a lower number of cells and to impaired G1/S cell cycle progression. eIF6(+/-) cells retain sufficient nucleolar eIF6 and normal ribosome biogenesis. The liver of eIF6(+/-) mice displays an increase of 80S in polysomal profiles, indicating a defect in initiation of translation. Consistently, isolated hepatocytes have impaired insulin-stimulated translation. Heterozygous mouse embryonic fibroblasts recapitulate the organism phenotype and have normal ribosome biogenesis, reduced insulin-stimulated translation, and delayed G1/S phase progression. Furthermore, eIF6(+/-) cells are resistant to oncogene-induced transformation. Thus, eIF6 is the first eIF associated with the large 60S subunit that regulates translation in response to extracellular signals. 相似文献
84.
Marscher AP Jorstad SG D'Arcangelo FD Smith PS Williams GG Larionov VM Oh H Olmstead AR Aller MF Aller HD McHardy IM Lähteenmäki A Tornikoski M Valtaoja E Hagen-Thorn VA Kopatskaya EN Gear WK Tosti G Kurtanidze O Nikolashvili M Sigua L Miller HR Ryle WT 《Nature》2008,452(7190):966-969
Blazars are the most extreme active galactic nuclei. They possess oppositely directed plasma jets emanating at near light speeds from accreting supermassive black holes. According to theoretical models, such jets are propelled by magnetic fields twisted by differential rotation of the black hole's accretion disk or inertial-frame-dragging ergosphere. The flow velocity increases outward along the jet in an acceleration and collimation zone containing a coiled magnetic field. Detailed observations of outbursts of electromagnetic radiation, for which blazars are famous, can potentially probe the zone. It has hitherto not been possible to either specify the location of the outbursts or verify the general picture of jet formation. Here we report sequences of high-resolution radio images and optical polarization measurements of the blazar BL Lacertae. The data reveal a bright feature in the jet that causes a double flare of radiation from optical frequencies to TeV gamma-ray energies, as well as a delayed outburst at radio wavelengths. We conclude that the event starts in a region with a helical magnetic field that we identify with the acceleration and collimation zone predicted by the theories. The feature brightens again when it crosses a standing shock wave corresponding to the bright 'core' seen on the images. 相似文献
85.
Warne T Serrano-Vega MJ Baker JG Moukhametzianov R Edwards PC Henderson R Leslie AG Tate CG Schertler GF 《Nature》2008,454(7203):486-491
G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 A resolution crystal structure of a beta(1)-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane alpha-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the beta(1)-adrenergic receptor and binding of carazolol to the beta(2)-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the beta(2)-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation. 相似文献
86.
Big data: The future of biocuration 总被引:2,自引:0,他引:2
Howe D Costanzo M Fey P Gojobori T Hannick L Hide W Hill DP Kania R Schaeffer M St Pierre S Twigger S White O Rhee SY 《Nature》2008,455(7209):47-50
87.
88.
Emma Langella Martina Buonanno Daniela Vullo Nina Dathan Marilisa Leone Claudiu T. Supuran Giuseppina De Simone Simona Maria Monti 《Cellular and molecular life sciences : CMLS》2018,75(17):3283-3296
Human carbonic anhydrase IX (hCA IX) is a tumour-associated enzyme present in a limited number of normal tissues, but overexpressed in several malignant human tumours. It is a transmembrane protein, where the extracellular region consists of a greatly investigated catalytic CA domain and a much less investigated proteoglycan-like (PG) domain. Considering its important role in tumour biology, here, we report for the first time the full characterization of the PG domain, providing insights into its structural and functional features. In particular, this domain has been produced at high yields in bacterial cells and characterized by means of biochemical, biophysical and molecular dynamics studies. Results show that it belongs to the family of intrinsically disordered proteins, being globally unfolded with only some local residual polyproline II secondary structure. The observed conformational flexibility may have several important roles in tumour progression, facilitating interactions of hCA IX with partner proteins assisting tumour spreading and progression. 相似文献
89.
Maria Luiza Beçak Kazumi Fukuda Pizzocaro 《Cellular and molecular life sciences : CMLS》1980,36(2):164-166
Summary Previtellogenic oocytes ofOdontophrynus americanus display hundreds of chromatin circles. Electron microscopy of spread preparations of isolated nuclei shows that the circles originate from the chromatin. The circles change their morphology and form new copies. The length of the DNA packed in the nucleosomal circles is about 2.5–3.5 m or multiples of this value. Assuming that histones need not be removed from chromatin before DNA replication3 we suggest that the circles might belong to the process of rDNA amplification.This work was supported by grants from the Brazilian CNPq, FAPESP and FEDIB.We thank Dr A. Brunner Jr for the use of the electron microscope and Dr N. Leon for his valuable help. 相似文献
90.
Serena Duchi Valeria Cavaliere Luca Fagnocchi Maria Rosaria Grimaldi Patrizia Falabella Franco Graziani Silvia Gigliotti Francesco Pennacchio Giuseppe Gargiulo 《Cellular and molecular life sciences : CMLS》2010,67(10):1699-1712
Polydnavirus-encoded IκB-like proteins are similar to insect and mammalian IκB, and an immunosuppressive function in the host
cells has been inferred to these proteins. Here we show that the expression of one of these IκB-like viral genes, the TnBVank1, in the Drosophila germline affects the localization of gurken, bicoid, and oskar mRNAs whose gene products are relevant for proper embryonic patterning. The altered localization of these mRNAs is suggestive
of general defects in the intracellular, microtubule-based, trafficking routes. Analysis of microtubule motor proteins components
such as the dynein heavy chain and the kinesin heavy chain revealed defects in the polarized microtubule network. Interestingly,
the TnBVANK1 viral protein is uniformly distributed over the entire oocyte cortex, and appears to be anchored to the microtubule
ends. Our data open up a very interesting issue on novel function(s) played by the ank gene family by interfering with cytoskeleton organization. 相似文献