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Nucleophosmin (NPM) (B23) is an essential protein in mouse development and cell growth; however, it has been assigned numerous roles in very diverse cellular processes. Here, we present a unified mechanism for NPM's role in cell growth; NPM directs the nuclear export of both 40S and 60S ribosomal subunits. NPM interacts with rRNA and large and small ribosomal subunit proteins and also colocalizes with large and small ribosomal subunit proteins in the nucleolus, nucleus, and cytoplasm. The transduction of NPM shuttling-defective mutants or the loss of Npm1 inhibited the nuclear export of both the 40S and 60S ribosomal subunits, reduced the available pool of cytoplasmic polysomes, and diminished overall protein synthesis without affecting rRNA processing or ribosome assembly. While the inhibition of NPM shuttling can block cellular proliferation, the dramatic effects on ribosome export occur prior to cell cycle inhibition. Modest increases in NPM expression amplified the export of newly synthesized rRNAs, resulting in increased rates of protein synthesis and indicating that NPM is rate limiting in this pathway. These results support the idea that NPM-regulated ribosome export is a fundamental process in cell growth.  相似文献   
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Salmena L  Carracedo A  Pandolfi PP 《Cell》2008,133(3):403-414
Since its discovery as the elusive tumor suppressor gene at the frequently mutated 10q23 locus, PTEN has been identified as lost or mutated in several sporadic and heritable tumor types. A decade of work has established that PTEN is a nonredundant phosphatase that is essential for regulating the highly oncogenic prosurvival PI3K/AKT signaling pathway. This review discusses emerging modes of PTEN function and regulation, and speculates about how manipulation of PTEN function could be used for cancer therapy.  相似文献   
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The enhancing effect of three marine bioactive substances (MBS) – EXT1116, NA9158 and 251104 – on the absorption of ammonium and potassium by the root system and the growth of potted grapevine (Vitis vinifera L.) plants is reported. Root ion influxes were determined in vivo by the non-invasive vibrating probe technique. Treatment with MBS generally enhanced nutrient absorption only in the root region between 0.8 and 1.7 mm from the root apex. Among the three substances tested, EXT1116 was the most effective in terms of enhancing the absorption of both ions, with significantly higher values than those of the other two substances and the control. NA9158 and 251104 were more effective in improving ammonium absorption than potassium absorption, while NA9158 was the most effective MBS in enhancing both biomorphometric parameters (shoot length, number of leaves, visual assessment of root system) and dry weight. Based on these results, we suggest that a combination of NA9158 and EXT1116 may be useful in enhancing plant growth by combining the capacity of NA9158 to increase root biomass and that of EXT1116 to enhance mineral absorption.  相似文献   
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Mouse models for multistep tumorigenesis.   总被引:3,自引:0,他引:3  
The mouse is an ideal model system for studying the molecular mechanisms underlying the pathogenesis of human cancer. The generation of transgenic and gene-knockout mice has been instrumental in determining the role of major determinants in this process, such as oncogenes and tumor-suppressor genes. In the past few years, modeling cancer in the mouse has increased in its complexity, allowing in vivo dissection of the fundamental concepts underlying cooperative oncogenesis in various tumor types. In this review, we discuss how this transition has been facilitated, providing relevant examples. We also review how, in the post-genome era, novel methodologies will further accelerate the study of multi-step tumorigenesis in the mouse.  相似文献   
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Understanding range limits is critical to predicting species responses to climate change. Subtropical environments, where many species overlap at their range margins, are cooler, more light‐limited and variable than tropical environments. It is thus likely that species respond variably to these multi‐stressor regimes and that factors other than mean climatic conditions drive biodiversity patterns. Here, we tested these hypotheses for scleractinian corals at their high‐latitude range limits in eastern Australia and investigated the role of mean climatic conditions and of parameters linked to abiotic stress in explaining the distribution and abundance of different groups of species. We found that environmental drivers varied among taxa and were predominantly linked to abiotic stress. The distribution and abundance of tropical species and gradients in species richness (alpha diversity) and turnover (beta diversity) were best explained by light limitation, whereas minimum temperatures and temperature fluctuations best explained gradients in subtropical species, species nestedness and functional diversity. Variation in community structure (considering species composition and abundance) was most closely linked to the combined thermal and light regime. Our study demonstrates the role of abiotic stress in controlling the distribution of species towards their high‐latitude range limits and suggests that, at biogeographic transition zones, robust predictions of the impacts of climate change require approaches that account for various aspects of physiological stress and for species abundances and characteristics. These findings support the hypothesis that abiotic stress controls high‐latitude range limits and caution that projections solely based on mean temperature could underestimate species’ vulnerabilities to climate change.  相似文献   
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