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61.
Homologous plant and bacterial proteins chaperone oligomeric protein assembly 总被引:190,自引:0,他引:190
S M Hemmingsen C Woolford S M van der Vies K Tilly D T Dennis C P Georgopoulos R W Hendrix R J Ellis 《Nature》1988,333(6171):330-334
An abundant chloroplast protein is implicated in the assembly of the oligomeric enzyme ribulose bisphosphate carboxylase-oxygenase, which catalyses photosynthetic CO2-fixation in higher plants. The product of the Escherichia coli groEL gene is essential for cell viability and is required for the assembly of bacteriophage capsids. Sequencing of the groEL gene and the complementary cDNA encoding the chloroplast protein has revealed that these proteins are evolutionary homologues which we term 'chaperonins'. Chaperonins comprise a class of molecular chaperones that are found in chloroplasts, mitochondria and prokaryotes. Assisted post-translational assembly of oligomeric protein structures is emerging as a general cellular phenomenon. 相似文献
62.
63.
E. D. Avner W. E. Sweeney Jr N. P. Piesco D. Ellis 《Cellular and molecular life sciences : CMLS》1986,42(1):77-80
Summary Cystic kidneys from the mutant CPK strain of C57BL/6J mice were cultured in serum-free organ culture. During 120 h of incubation in chemically-defined medium, CPK cystic tubular changes underwent complete regression. Environmental factors regulate the expression of genetically determined polycystic kidney disease in this model. 相似文献
64.
Whether or not the Large Hadron Collider reveals the long-awaited Higgs particle, it is likely to lead to discoveries that add to, or challenge, the standard model of particle physics. Data produced will be pored over for any evidence of supersymmetric partners for the existing denizens of the particle 'zoo' and for the curled-up extra dimensions demanded by string theory. There might also be clues as to why matter dominates over antimatter in the Universe, and as to the nature of the Universe's dark matter. 相似文献
65.
Logan CV Lucke B Pottinger C Abdelhamed ZA Parry DA Szymanska K Diggle CP van Riesen A Morgan JE Markham G Ellis I Manzur AY Markham AF Shires M Helliwell T Scoto M Hübner C Bonthron DT Taylor GR Sheridan E Muntoni F Carr IM Schuelke M Johnson CA 《Nature genetics》2011,43(12):1189-1192
Infantile myopathies with diaphragmatic paralysis are genetically heterogeneous, and clinical symptoms do not assist in differentiating between them. We used phased haplotype analysis with subsequent targeted exome sequencing to identify MEGF10 mutations in a previously unidentified type of infantile myopathy with diaphragmatic weakness, areflexia, respiratory distress and dysphagia. MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers, which are greatly reduced in muscle from individuals with early onset myopathy, areflexia, respiratory distress and dysphagia. 相似文献
66.
Ellis JA 《Cellular and molecular life sciences : CMLS》2006,63(23):2702-2709
Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular degenerative condition with an associated dilated cardiomyopathy
and cardiac conduction defect. It can be inherited in either an X-linked or autosomal manner by mutations in the nuclear proteins
emerin and lamin A/C, respectively. Traditionally muscular dystrophies were associated with defects in sarcolemma-associated
proteins and, therefore, a nuclear connection suggested the existence of novel signalling pathways associated with this group
of diseases. Subsequently, other mutations in the lamin A/C gene were attributed to a range of tissue-specific degenerative
conditions, collectively known as the ‘laminopathies’. Therefore, any proposed hypothesis underlying the molecular mechanism
of EDMD needs to include this anomaly. As we celebrate the 10th anniversary of the identification of emerin as a component
of the nuclear envelope, I discuss here the available evidence that currently implicates EDMD as arising from perturbations
in myogenic regulatory pathways, causing temporal delays in both cell cycle progression and muscle regeneration.
Received 25 May 2006; received after revision 22 June 2006; accepted 22 August 2006 相似文献
67.
Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing 总被引:1,自引:0,他引:1
Stark MS Woods SL Gartside MG Bonazzi VF Dutton-Regester K Aoude LG Chow D Sereduk C Niemi NM Tang N Ellis JJ Reid J Zismann V Tyagi S Muzny D Newsham I Wu Y Palmer JM Pollak T Youngkin D Brooks BR Lanagan C Schmidt CW Kobe B MacKeigan JP Yin H Brown KM Gibbs R Trent J Hayward NK 《Nature genetics》2012,44(2):165-169
We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predicted that mutations in the kinase domain may affect the activity and regulation of these protein kinases. The position of the mutations and the loss of heterozygosity of MAP3K5 and MAP3K9 in 85% and 67% of melanoma samples, respectively, together suggest that the mutations are likely to be inactivating. In in vitro kinase assays, MAP3K5 I780F and MAP3K9 W333* variants had reduced kinase activity. Overexpression of MAP3K5 or MAP3K9 mutants in HEK293T cells reduced the phosphorylation of downstream MAP kinases. Attenuation of MAP3K9 function in melanoma cells using siRNA led to increased cell viability after temozolomide treatment, suggesting that decreased MAP3K pathway activity can lead to chemoresistance in melanoma. 相似文献
68.
Fairfax BP Makino S Radhakrishnan J Plant K Leslie S Dilthey A Ellis P Langford C Vannberg FO Knight JC 《Nature genetics》2012,44(5):502-510
Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10(-15)), PRIC285 (P = 3.0 × 10(-10)) and an upstream region of CDKN1A (P = 2 × 10(-52)), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type-specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility. 相似文献
69.
70.
Walter F Decarli R Carilli C Bertoldi F Cox P Da Cunha E Daddi E Dickinson M Downes D Elbaz D Ellis R Hodge J Neri R Riechers DA Weiss A Bell E Dannerbauer H Krips M Krumholz M Lentati L Maiolino R Menten K Rix HW Robertson B Spinrad H Stark DP Stern D 《Nature》2012,486(7402):233-236
The Hubble Deep Field provides one of the deepest multiwavelength views of the distant Universe and has led to the detection of thousands of galaxies seen throughout cosmic time. An early map of the Hubble Deep Field at a wavelength of 850?micrometres, which is sensitive to dust emission powered by star formation, revealed the brightest source in the field, dubbed HDF?850.1 (ref. 2). For more than a decade, and despite significant efforts, no counterpart was found at shorter wavelengths, and it was not possible to determine its redshift, size or mass. Here we report a redshift of z = 5.183 for HDF?850.1, from a millimetre-wave molecular line scan. This places HDF?850.1 in a galaxy overdensity at z?≈?5.2, corresponding to a cosmic age of only 1.1?billion years after the Big Bang. This redshift is significantly higher than earlier estimates and higher than those of most of the hundreds of submillimetre-bright galaxies identified so far. The source has a star-formation rate of 850 solar masses per year and is spatially resolved on scales of 5 kiloparsecs, with an implied dynamical mass of about 1.3?×?10(11) solar masses, a significant fraction of which is present in the form of molecular gas. Despite our accurate determination of redshift and position, a counterpart emitting starlight remains elusive. 相似文献