RESUMO
Tumor-suppressor p53 is frequently mutated in human cancers. Many tumor-associated mutant p53 (mutp53) proteins gain new functions in promoting tumorigenesis, defined as gain-of-function (GOF). The mechanisms for mutp53 GOF are not well understood. Here, we report Pontin, a highly conserved AAA+ ATPase important for various cellular functions, as a new mutp53-binding protein. This Pontin-mutp53 interaction promotes mutp53 GOF in invasion, migration and anchorage-independent growth of tumor cells. The ATPase domain of Pontin is crucial for its promoting effect on mutp53 GOF; blocking the ATPase activity of Pontin by a Pontin-specific ATPase inhibitor or an ATPase-deficient dominant-negative Pontin expression vector greatly diminished mutp53 GOF. Pontin promotes mutp53 GOF through regulation of mutp53 transcriptional activity; knockdown of Pontin abolished the transcriptional regulation of mutp53 toward a group of genes. Furthermore, overexpression of Pontin in tumors is associated with the poor survival in cancer patients, especially those containing mutp53. Our results highlight an important role and mechanism for Pontin, a new mutp53 partner, in promoting mutp53 GOF in tumorigenesis.
Assuntos
Carcinogênese/metabolismo , Proteínas de Transporte/metabolismo , DNA Helicases/metabolismo , Proteína Supressora de Tumor p53/metabolismo , ATPases Associadas a Diversas Atividades Celulares , Animais , Apoptose/genética , Apoptose/fisiologia , Carcinogênese/genética , Proteínas de Transporte/genética , Ciclo Celular/genética , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/genética , Movimento Celular/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Imunoprecipitação da Cromatina , DNA Helicases/genética , Células HCT116 , Humanos , Técnicas In Vitro , Camundongos , Mutação/genética , Ligação Proteica/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Data on comparative investigations of chemical structure of lignins from medical grassy plants Rhodiola rosea and Serratula coronata lignins were obtained. The NMR and ESR spectroscopy, and functional and element analysis were used. The high antioxidant activity of lignins was shown. Experimental evidence of anti-aging activity of Rhodiola rosea lignin on model objects Drosophila melanogaster were presented.
Assuntos
Antioxidantes , Asteraceae/química , Lignina , Rhodiola/química , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Interpretação Estatística de Dados , Drosophila/efeitos dos fármacos , Drosophila/crescimento & desenvolvimento , Feminino , Radicais Livres/química , Lignina/química , Lignina/isolamento & purificação , Lignina/farmacologia , Longevidade/efeitos dos fármacos , Masculino , Estrutura Molecular , Picratos/química , Relação Estrutura-AtividadeRESUMO
We have discovered spectacular patterns formed by drying aqueous drops of sodium poly(styrene sulfonate) containing fixed amounts of sodium chloride. Crystallization of salt molecules takes place at a critical concentration and several factors such as the polyelectrolyte concentration and humidity affect the final patterns formed. The observed patterns include concentric rings, needle-like structures, chains of triangular-shaped crystallites, etc. We describe the observed phenomenology accompanied by a theoretical model for the occurrence of concentric rings.
RESUMO
Quantitative and qualitative changes in the content of elements in the solid and liquid phases occurred as the pulp moved through fermenters during biooxidation of an ore flotation concentrate. The association of microorganisms were adapted for utilizing sulfur-containing substrates; however, the rate of their oxidation was insufficient, which led to an increase in the amount of sodium cyanide required for gold recovery. The replacement of one-fourth of the liquid phase of the pulp (density, 13%) with a mineral medium without an energy source, the fractional addition of FeSO4 x 7H2O (1 g/l per day), and the improvement of pulp aeration made it possible to increase the content of SO4(2-) by 80.7, 86.2, and 58.5%, respectively. When one-fourth of the liquid phasa of the pulp (density, 24%) was replaced with a mineral medium without an energy source, the rate of additional oxidation of sulfide minerals increased, which increased the efficiency of gold extraction into solution and gold recovery on charcoal by 3.4 and 3.6%, respectively, and reduced sodium cyanide consumption by 3 kg/ton.
Assuntos
Bactérias/crescimento & desenvolvimento , Ouro/isolamento & purificação , Sulfatos/metabolismo , Ouro/química , Concentração de Íons de Hidrogênio , Oxirredução , Cianeto de Sódio/química , Sulfatos/químicaRESUMO
We report hitherto unrecognized cooperative behavior in the stochastic collapse of certain compressed lipid monolayers implicated in pulmonary function. The cooperativity emerges from a statistical analysis of the collapse events captured using fluorescence microscopy and digital image analysis. The collapse events involve folding of the monolayer on a micron scale, yet each event produces a macroscopic jerk of the layer. The cooperative collapse is striking for its temporal sharpness and large spatial extent.
