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Mutations of the BRAF gene in human cancer 总被引:2,自引:0,他引:2
Davies H Bignell GR Cox C Stephens P Edkins S Clegg S Teague J Woffendin H Garnett MJ Bottomley W Davis N Dicks E Ewing R Floyd Y Gray K Hall S Hawes R Hughes J Kosmidou V Menzies A Mould C Parker A Stevens C Watt S Hooper S Wilson R Jayatilake H Gusterson BA Cooper C Shipley J Hargrave D Pritchard-Jones K Maitland N Chenevix-Trench G Riggins GJ Bigner DD Palmieri G Cossu A Flanagan A Nicholson A Ho JW Leung SY Yuen ST Weber BL Seigler HF Darrow TL Paterson H Marais R Marshall CJ Wooster R 《Nature》2002,417(6892):949-954
Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma. 相似文献
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R. J. Capon K. Elsbury M. S. Butler C. C. Lu J. N. A. Hooper J. A. P. Rostas K. J. O'Brien L. -M. Mudge A. T. R. Sim 《Cellular and molecular life sciences : CMLS》1993,49(3):263-264
The Antarctic marine spongeTedania charcoti has been shown to contain extraordinarily high natural concentrations of cadmium and zinc, which have in turn been correlated to the ability of the crude ethanol extract to modulate protein phosphorylation in chicken forebrain and to inhibit the growth of several test bacteria. 相似文献
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K. R. Weiss V. Březina E. C. Cropper S. L. Hooper M. W. Miller W. C. Probst F. S. Vilim I. Kupfermann 《Cellular and molecular life sciences : CMLS》1992,48(5):456-463
Despite their ubiquitous presence in the central and peripheral nervous systems, the behavioral functions of peptide co-transmitters remain to be elucidated. The marine molluscAplysia, whose simple nervous system facilitates the study of the neural basis of behavior, was used to investigate the role of peptidergic co-transmission in feeding behavior. Several novel modulatory neuropeptides were purified, and localized to identified cholinergic motorneurons. Physiological and biochemical studies demonstrated that these peptides are released when the motorneourons fire at frequencies that occur during normal behavior, and that the peptides modify the relationship between muscle contraction amplitude and relaxation rate so as to maintain optimal motor output when the intensity and frequency of feeding behavior change. 相似文献
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Proteome survey reveals modularity of the yeast cell machinery 总被引:4,自引:0,他引:4
Gavin AC Aloy P Grandi P Krause R Boesche M Marzioch M Rau C Jensen LJ Bastuck S Dümpelfeld B Edelmann A Heurtier MA Hoffman V Hoefert C Klein K Hudak M Michon AM Schelder M Schirle M Remor M Rudi T Hooper S Bauer A Bouwmeester T Casari G Drewes G Neubauer G Rick JM Kuster B Bork P Russell RB Superti-Furga G 《Nature》2006,440(7084):631-636
Protein complexes are key molecular entities that integrate multiple gene products to perform cellular functions. Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. Through systematic tagging of open reading frames (ORFs), the majority of complexes were purified several times, suggesting screen saturation. The richness of the data set enabled a de novo characterization of the composition and organization of the cellular machinery. The ensemble of cellular proteins partitions into 491 complexes, of which 257 are novel, that differentially combine with additional attachment proteins or protein modules to enable a diversification of potential functions. Support for this modular organization of the proteome comes from integration with available data on expression, localization, function, evolutionary conservation, protein structure and binary interactions. This study provides the largest collection of physically determined eukaryotic cellular machines so far and a platform for biological data integration and modelling. 相似文献
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Targetted correction of a mutant HPRT gene in mouse embryonic stem cells 总被引:11,自引:0,他引:11
T Doetschman R G Gregg N Maeda M L Hooper D W Melton S Thompson O Smithies 《Nature》1987,330(6148):576-578
Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells that can still enter the germline after genetic manipulation in culture and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DAN can be used in culture to modify specifically the target locus. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways. 相似文献