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41.
Protein synthesis required to anchor a mutant p53 protein which is temperature-sensitive for nuclear transport 总被引:21,自引:0,他引:21
The p53 protein is rendered temperature-sensitive by a point mutation. Rat cells transformed by this mutant p53 and an activated ras oncogene grow well at 37 degrees C but cease DNA synthesis and cell division when shifted to 32 degrees C. Immunostaining demonstrates that the mutant p53 protein is in the nucleus of the arrested cells at 32 degrees C but in the cytoplasm of the growing cells at 37 degrees C. This is the first example of a protein which is temperature-sensitive for nuclear transport. The translocation from cytoplasm to nucleus and vice versa occurs 6 h after temperature shift and is coincident with the inhibition of DNA synthesis; transport from cytoplasm to nucleus does not require protein synthesis. Remarkably, inhibition of protein synthesis at 37 degrees C also results in the rapid appearance of mutant p53 in the cell nucleus. These results suggest the presence of a short-lived protein responsible for holding p53 in the cytoplasm at 37 degrees C but not at 32 degrees C. Analysis of a non-temperature-sensitive mutant p53 protein shows that its cytoplasmic location is sensitive to protein synthesis inhibitors but not to temperature. 相似文献
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Araki T Enomoto S Furuno K Gando Y Ichimura K Ikeda H Inoue K Kishimoto Y Koga M Koseki Y Maeda T Mitsui T Motoki M Nakajima K Ogawa H Ogawa M Owada K Ricol JS Shimizu I Shirai J Suekane F Suzuki A Tada K Takeuchi S Tamae K Tsuda Y Watanabe H Busenitz J Classen T Djurcic Z Keefer G Leonard D Piepke A Yakushev E Berger BE Chan YD Decowski MP Dwyer DA Freedman SJ Fujikawa BK Goldman J Gray F Heeger KM Hsu L Lesko KT Luk KB Murayama H O'Donnell T Poon AW Steiner HM Winslow LA Mauger C McKeown RD 《Nature》2005,436(7050):499-503
The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained. 相似文献
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Cepheids are a class of variable (pulsating) stars whose absolute luminosities are related in a simple manner to their pulsational periods. By measuring the period and using the 'period-luminosity' relationship, astronomers can use the observed visual brightness to determine the distance to the star. Because these stars are very luminous, they can be observed in other galaxies, and therefore can be used to help determine the expansion rate of the Universe (the Hubble constant). Calibration of the period-luminosity relation is a necessary first step, but the small number of sufficiently nearby Cepheids has forced the use of a number of indirect means, with associated systematic uncertainties. Here we present a distance to the Cepheid zeta Geminorum, determined using a direct measurement (by an optical interferometer) of its changes in diameter as it pulsates. Within our uncertainty of 15 per cent, our distance is in agreement with previous indirect determinations. Planned improvements to the instrument will allow us to calibrate directly the period-luminosity relation to better than a few per cent. 相似文献
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Goudie DR D'Alessandro M Merriman B Lee H Szeverényi I Avery S O'Connor BD Nelson SF Coats SE Stewart A Christie L Pichert G Friedel J Hayes I Burrows N Whittaker S Gerdes AM Broesby-Olsen S Ferguson-Smith MA Verma C Lunny DP Reversade B Lane EB 《Nature genetics》2011,43(4):365-369
Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars. High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer. 相似文献
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Snape K Hanks S Ruark E Barros-Núñez P Elliott A Murray A Lane AH Shannon N Callier P Chitayat D Clayton-Smith J Fitzpatrick DR Gisselsson D Jacquemont S Asakura-Hay K Micale MA Tolmie J Turnpenny PD Wright M Douglas J Rahman N 《Nature genetics》2011,43(6):527-529
Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division. 相似文献
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Turnbull C Perdeaux ER Pernet D Naranjo A Renwick A Seal S Munoz-Xicola RM Hanks S Slade I Zachariou A Warren-Perry M Ruark E Gerrard M Hale J Hewitt M Kohler J Lane S Levitt G Madi M Morland B Neefjes V Nicholdson J Picton S Pizer B Ronghe M Stevens M Traunecker H Stiller CA Pritchard-Jones K Dome J Grundy P Rahman N 《Nature genetics》2012,44(6):681-684
Wilms tumor is the most common renal malignancy of childhood. To identify common variants that confer susceptibility to Wilms tumor, we conducted a genome-wide association study in 757 individuals with Wilms tumor (cases) and 1,879 controls. We evaluated ten SNPs in regions significantly associated at P < 5 × 10(-5) in two independent replication series from the UK (769 cases and 2,814 controls) and the United States (719 cases and 1,037 controls). We identified clear significant associations at 2p24 (rs3755132, P = 1.03 × 10(-14); rs807624, P = 1.32 × 10(-14)) and 11q14 (rs790356, P = 4.25 × 10(-15)). Both regions contain genes that are plausibly related to Wilms tumorigenesis. We also identified candidate association signals at 5q14, 22q12 and Xp22. 相似文献