排序方式: 共有9条查询结果,搜索用时 31 毫秒
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Synthetic insecticide with a new order of activity 总被引:5,自引:0,他引:5
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Hsieh AC Liu Y Edlind MP Ingolia NT Janes MR Sher A Shi EY Stumpf CR Christensen C Bonham MJ Wang S Ren P Martin M Jessen K Feldman ME Weissman JS Shokat KM Rommel C Ruggero D 《Nature》2012,485(7396):55-61
The mammalian target of rapamycin (mTOR) kinase is a master regulator of protein synthesis that couples nutrient sensing to cell growth and cancer. However, the downstream translationally regulated nodes of gene expression that may direct cancer development are poorly characterized. Using ribosome profiling, we uncover specialized translation of the prostate cancer genome by oncogenic mTOR signalling, revealing a remarkably specific repertoire of genes involved in cell proliferation, metabolism and invasion. We extend these findings by functionally characterizing a class of translationally controlled pro-invasion messenger RNAs that we show direct prostate cancer invasion and metastasis downstream of oncogenic mTOR signalling. Furthermore, we develop a clinically relevant ATP site inhibitor of mTOR, INK128, which reprograms this gene expression signature with therapeutic benefit for prostate cancer metastasis, for which there is presently no cure. Together, these findings extend our understanding of how the 'cancerous' translation machinery steers specific cancer cell behaviours, including metastasis, and may be therapeutically targeted. 相似文献
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Stewart W. Janes 《西北部美国博物学家》2011,63(3)
Populations of breeding Swainson's Hawks ( Buteo swainsoni ), Red-tailed Hawks ( B. jamaicensis ), and Golden Eagles ( Aquila chrysaetos ) present in 1999 were compared with populations present between 1975 and 1982 at a 129-km 2 site in north central Oregon. Populations of Red-tailed Hawks and Golden Eagles remained unchanged, but the number of Swainson's Hawks pairs increased from 15 to 17. In 1999 Golden Eagles used nests occupied between 1975 and 1982, and 7 of 31 pairs of Red-tailed Hawks used nests occupied in earlier years. No Swainson's Hawks nested in trees occupied earlier. Few changes in territorial boundaries were detected. 相似文献
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Alföldi J Di Palma F Grabherr M Williams C Kong L Mauceli E Russell P Lowe CB Glor RE Jaffe JD Ray DA Boissinot S Shedlock AM Botka C Castoe TA Colbourne JK Fujita MK Moreno RG ten Hallers BF Haussler D Heger A Heiman D Janes DE Johnson J de Jong PJ Koriabine MY Lara M Novick PA Organ CL Peach SE Poe S Pollock DD de Queiroz K Sanger T Searle S Smith JD Smith Z Swofford R Turner-Maier J Wade J Young S Zadissa A Edwards SV Glenn TC Schneider CJ Losos JB Lander ES Breen M Ponting CP Lindblad-Toh K 《Nature》2011,477(7366):587-591
The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations. 相似文献
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A photostable pyrethroid 总被引:4,自引:0,他引:4
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The fundamental components of many signalling pathways are common to all cells. However, stimulating or perturbing the intracellular network often causes distinct phenotypes that are specific to a given cell type. This 'cell specificity' presents a challenge in understanding how intracellular networks regulate cell behaviour and an obstacle to developing drugs that treat signalling dysfunctions. Here we apply a systems-modelling approach to investigate how cell-specific signalling events are integrated through effector proteins to cause cell-specific outcomes. We focus on the synergy between tumour necrosis factor and an adenoviral vector as a therapeutically relevant stimulus that induces cell-specific responses. By constructing models that estimate how kinase-signalling events are processed into phenotypes through effector substrates, we find that accurate predictions of cell specificity are possible when different cell types share a common 'effector-processing' mechanism. Partial-least-squares regression models based on common effector processing accurately predict cell-specific apoptosis, chemokine release, gene induction, and drug sensitivity across divergent epithelial cell lines. We conclude that cell specificity originates from the differential activation of kinases and other upstream transducers, which together enable different cell types to use common effectors to generate diverse outcomes. The common processing of network signals by downstream effectors points towards an important cell biological principle, which can be applied to the understanding of cell-specific responses to targeted drug therapies. 相似文献
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Numerous studies attest to essential roles for Eph receptors and their ephrin ligands in controlling cell positioning and tissue patterning during normal and oncogenic development. These studies suggest multiple, sometimes contradictory, functions of Eph-ephrin signalling, which under different conditions can promote either spreading and cell-cell adhesion or cytoskeletal collapse, cell rounding, de-adhesion and cell-cell segregation. A principle determinant of the balance between these two opposing responses is the degree of receptor/ligand clustering and activation. This equilibrium is likely altered in cancers and modulated by somatic mutations of key Eph family members that have emerged as candidate cancer markers in recent profiling studies. In addition, cross-talk amongst Ephs and with other signalling pathways significantly modulates cell-cell adhesion, both between and within Eph- and ephrin-expressing cell populations. This review summarises our current understanding of how Eph receptors control cell adhesion and morphology, and presents examples demonstrating the importance of these events in normal development and cancer. 相似文献
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