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81.
PML regulates p53 stability by sequestering Mdm2 to the nucleolus 总被引:12,自引:0,他引:12
Bernardi R Scaglioni PP Bergmann S Horn HF Vousden KH Pandolfi PP 《Nature cell biology》2004,6(7):665-672
The promyelocytic leukaemia (PML) tumour-suppressor protein potentiates p53 function by regulating post-translational modifications, such as CBP-dependent acetylation and Chk2-dependent phosphorylation, in the PML-Nuclear Body (NB). PML was recently shown to interact with the p53 ubiquitin-ligase Mdm2 (refs 4-6); however, the mechanism by which PML regulates Mdm2 remains unclear. Here, we show that PML enhances p53 stability by sequestering Mdm2 to the nucleolus. We found that after DNA damage, PML and Mdm2 accumulate in the nucleolus in an Arf-independent manner. In addition, we found that the nucleolar localization of PML is dependent on ATR activation and phosphorylation of PML by ATR. Notably, in Pml(-/-) cells, sequestration of Mdm2 to the nucleolus was impaired, as well as p53 stabilization and the induction of apoptosis. Furthermore, we demonstrate that PML physically associates with the nucleolar protein L11, and that L11 knockdown impairs the ability of PML to localize to nucleoli after DNA damage. These findings demonstrate an unexpected role of PML in the nucleolar network for tumour suppression. 相似文献
82.
Structure of foot-and-mouth disease virus RNA-dependent RNA polymerase and its complex with a template-primer RNA 总被引:15,自引:0,他引:15
Ferrer-Orta C Arias A Perez-Luque R Escarmís C Domingo E Verdaguer N 《The Journal of biological chemistry》2004,279(45):47212-47221
Genome replication in picornaviruses is catalyzed by a virally encoded RNA-dependent RNA polymerase, termed 3D. The enzyme performs this operation, together with other viral and probably host proteins, in the cytoplasm of their host cells. The crystal structure of the 3D polymerase of foot-and-mouth disease virus, one of the most important animal pathogens, has been determined unliganded and bound to a template-primer RNA decanucleotide. The enzyme folds in the characteristic fingers, palm and thumb subdomains, with the presence of an NH2-terminal segment that encircles the active site. In the complex, several conserved amino acid side chains bind to the template-primer, likely mediating the initiation of RNA synthesis. The structure provides essential information for studies on RNA replication and the design of antiviral compounds. 相似文献
83.
Y Blouquit M D Rhoda J Delanoe-Garin R Rosa J C Prome C Poyart G Puzo J M Bernassau J Rosa 《The Journal of biological chemistry》1986,261(15):6758-6764
A new minor Hb fraction initially designated Hbx, has been found in the hemolysate of an erythremic patient that we have previously described with a complete erythrocyte bisphosphoglycerate mutase (EC 5.4.2.4) deficiency. Hbx (3.5% of the total) was detected by isoelectric focusing and exhibited electrophoretic and chromatographic properties similar to those of several variants of the Hb central cavity. By density fractionation of red cells, it was demonstrated that Hbx was an aging hemoglobin as in the case of glycated Hb A1c. Functional studies revealed a low oxygen affinity and almost complete inhibition of the allosteric effect of the organic phosphate effectors. Structural studies demonstrated an absence of tryptic cleavage between the peptides beta T9 and beta T10 suggesting the presence of an adduct on Lys beta 82 or on a neighboring residue. Fast atom bombardment mass spectrometry and a specific enzymatic assay with glyoxylate reductase demonstrated that the beta 82 adduct was a glycerate moiety. It was concluded that Hbx was a glycerylated Hb, alpha 2A beta 2(82) (EF6) N epsilon-glyceryllysine, to our knowledge the first example of glycerylated protein. The mechanism of formation of glyceryl Hb, which was found in the four studied subjects with a bisphosphoglyceromutase deficiency, remains to be determined. 相似文献
84.
Simone V. Generoso Mirelle Viana Rosana Santos Flaviano S. Martins José A. N. Machado Rosa M. E. Arantes Jacques R. Nicoli Maria I. T. D. Correia Valbert N. Cardoso 《Archives of microbiology》2010,192(6):477-484
Probiotic is a preparation containing microorganisms that confers beneficial effect to the host. This work assessed whether
oral treatment with viable or heat-killed yeast Saccharomyces cerevisiae strain UFMG 905 prevents bacterial translocation (BT), intestinal barrier integrity, and stimulates the immunity, in a murine
intestinal obstruction (IO) model. Four groups of mice were used: mice undergoing only laparotomy (CTL), undergoing intestinal
obstruction (IO) and undergoing intestinal obstruction after previous treatment with viable or heat-killed yeast. BT, determined
as uptake of 99mTc-E. coli in blood, mesenteric lymph nodes, liver, spleen and lungs, was significantly higher in IO group than in CTL group. Treatments
with both yeasts reduced BT in blood and all organs investigated. The treatment with both yeasts also reduced intestinal permeability
as determined by blood uptake of 99mTc-DTPA. Immunological data demonstrated that both treatments were able to significantly increase IL-10 levels, but only viable
yeast had the same effect on sIgA levels. Intestinal lesions were more severe in IO group when compared to CTL and yeasts
groups. Concluding, both viable and heat-killed cells of yeast prevent BT, probably by immunomodulation and by maintaining
gut barrier integrity. Only the stimulation of IgA production seems to depend on the yeast viability. 相似文献
85.
Sandra M. Vergamini Rosa M. Valencia-Barrera Barbara Catarina de Antoni Zoppas Carmen Pérez Morales Delia Fernández-González 《Aerobiologia》2006,22(2):141-148
An aerobiological study has been carried out in the region of Caxias do Sul in southern Brazil. Pollen monitoring was performed from January 1, 2001 through to December 31, 2002. A total of 30,469 pollen grains were collected during this period, and 40 pollen types were identified; of these, 23,389 pollen grains, representing 29 pollen types, originated from tree and shrub taxa. The maximum pollen concentration was registered in August 2001 and October 2002. In the study area, the pollen type Mimosa scabrella (18.8%) was much more abundant than all of the pollen types from tree and shrub taxa, such as: Urticaceae (18.4%), Myrtaceae (10.2%), Cupressaceae (7.7%), Myrsine (4.8%), Sorocea (3.9%), Pinaceae (2.9%), Asteraceae (2.2%) and Ricinus (2.1%). These nine pollen types accounted for the largest pollen concentrations of all the tree and shrub taxa. The pollen types Carya, Melastomataceae, Mimosa scabrella, Myrsine and Sorocea are reported for the first time in an aerobiological study in Brazil. 相似文献
86.
Rosa Gómez M. Isabel Arce J. Javier Sánchez M. del Mar Sánchez-Montoya 《Hydrobiologia》2012,679(1):43-59
Mediterranean climates predispose aquatic systems to both flood and drought periods, therefore, stream sediments may be exposed
to desiccation periods. Changes in oxygen concentrations and sediment water content influence the biotic processes implicated
in nitrogen dynamics. The objectives of this study were to identify (1) the changes of inorganic nitrogen in stream sediments
during the transition from wet to dry conditions, and (2) the underlying processes in N dynamics and its regulation. Extractable
sediment NO3
−-N and NH4
+-N, organic matter and extractable organic carbon content were assessed during natural desiccation in microcosms with sediments
from an intermittent Mediterranean stream. In agreement with our initial hypothesis, our results showed how the NO3
−-N content of the sediment was enhanced during the first 10 days of sediment drying, whereas NH4
+-N was lost by 14 days post-drying. During the first 10 days, sediment desiccation seemed to stimulate the net N-mineralization
and net nitrification from sediments. Afterwards, the extractable NO3
−-N concentration sharply dropped, which may be attributed to lower ammonium-oxidation rates as ammonium and organic matter
are depleted, and to an increase in NO3
−-N consumption by microbial populations. Denitrification was inhibited, with a significant decrease as % water-filled pore
space lowered. We hypothesize that the sediment inorganic N content enhanced during sediment desiccation could be released
as part of the N pulse observed after sediment rewetting. However, the stream N availability after rewetting dried sediments
would differ depending on desiccation period duration. 相似文献
87.
In March 2009, we documented the death of one member of a triplet polar bear (Ursus maritimus) litter at its den site in the southern Beaufort Sea (SBS) of Alaska. We used a self-contained video camera unit to document
activity between den emergence and departure. All three cubs showed low activity levels relative to other cubs observed, and
one died within one week of den emergence. Necropsy confirmed that the dead cub had a low body weight and was malnourished.
Capture later confirmed that the two surviving cubs were also undersized. Polar bear cub survival is influenced by many factors
including litter size and sea ice conditions. Triplet litters are often smaller and suffer higher mortality rates than singletons
and twins. This cub was not only a triplet but also born following 2 years of record minimum sea ice extent, both of which
may have played a role in this cub’s demise. 相似文献
88.
Rosa María Ferraz Escarlata Rodríguez‐Carmona Neus Ferrer‐Miralles Andreas Meyerhans Antonio Villaverde 《Journal of molecular recognition : JMR》2009,22(3):255-260
We have analyzed the suitability of six antigenic peptides from several HIV‐1 structural proteins (namely gp41, gp120, p17, and p24), as anti‐HIV‐1 antibody receptors in an allosteric enzymatic biosensor. These peptides were inserted in a solvent‐exposed surface of Escherichia coli (E. coli) beta‐galactosidase by means of conventional recombinant DNA technology. The resulting enzymes were tested to allosterically respond to sera from HIV‐1‐infected individuals. Only stretches from gp41 and gp120 envelope proteins were able to transduce the molecular contact signal in the presence of immunoreactive sera. Intriguingly, the enzyme displaying the CD4 binding site segment KQFINMWQEVGKAMYAPP was activated by soluble CD4, suggesting that it produces conformational modifications on the allosteric enzyme as those occurring during antibody‐promoted induced fit. This fact is discussed in the context of the design of smart protein drugs and markers targeted to CD4+ cells. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
89.
Tássio Benazzi Selma Calgaroto Viviane Astolfi Clarissa Dalla Rosa J. Vladimir Oliveira Marcio A. Mazutti 《Enzyme and microbial technology》2013,52(4-5):247-250
This work evaluates the pretreatment of sugarcane bagasse combining supercritical carbon dioxide (SC-CO2) and ultrasound to enhance the enzymatic hydrolysis of pretreated bagasse. In a first step the influence of process variables on the SC-CO2 pretreatment to enhance the enzymatic hydrolysis was evaluated by mean of a Plackett–Burmann design. Then, the sequential treatment combining ultrasound + SC-CO2 was evaluated. Results show that treatment using SC-CO2 increased the amount of fermentable sugar obtained of about 280% compared with the non-treated bagasse, leading to a hydrolysis efficiency (based on the amount of cellulose) as high as 74.2%. Combining ultrasound + SC-CO2 treatment increased about 16% the amount of fermentable sugar obtained by enzymatic hydrolysis in comparison with the treatment using only ultrasound. From the results presented in this work it can be concluded that the combined ultrasound + SC-CO2 treatment is an efficient and promising alternative to carry out the pretreatment of lignocellulosic feedstock at relatively low temperatures without the use of hazardous solvents. 相似文献
90.
Albert Flexas Jaume Rosselló Julia F. Christensen Marcos Nadal Antonio Olivera La Rosa Enric Munar 《PloS one》2013,8(11)
We examined the influence of affective priming on the appreciation of abstract artworks using an evaluative priming task. Facial primes (showing happiness, disgust or no emotion) were presented under brief (Stimulus Onset Asynchrony, SOA = 20ms) and extended (SOA = 300ms) conditions. Differences in aesthetic liking for abstract paintings depending on the emotion expressed in the preceding primes provided a measure of the priming effect. The results showed that, for the extended SOA, artworks were liked more when preceded by happiness primes and less when preceded by disgust primes. Facial expressions of happiness, though not of disgust, exerted similar effects in the brief SOA condition. Subjective measures and a forced-choice task revealed no evidence of prime awareness in the suboptimal condition. Our results are congruent with findings showing that the affective transfer elicited by priming biases evaluative judgments, extending previous research to the domain of aesthetic appreciation. 相似文献