Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
1.
Pathol Int ; 67(12): 597-601, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29047227

RESUMEN

High rates of telomerase reverse transcriptase (TERT) promoter mutations have recently been described in urothelial carcinoma (UC). Unlike UC in the bladder, adenocarcinomas account for the majority of urachal cancer (UrC) cases. As data in UrC is unclear, we analyzed TERT promoter mutations in a large cohort of UrC for its differential diagnostic, clinicopathological and prognostic significance. UrC cases from six academic centers were analyzed for c.-146C>T (C250T) and c.-124C>T (C228T) TERT promoter mutations by PCR and Sanger sequencing. Clinicopathological and survival data were collected. The cohort consisted of 15 men (56%) and 12 women (44%) with a median age of 50 years including 23 adenocarcinomas, two squamous cell carcinomas (SCC), one UC and one undifferentiated carcinoma. In one case of (mucinous) urachal adenocarcinoma a C228T mutation was detected (1/23; 4%), like in a case of SCC in addition to one C250T mutation in the UC case. TERT promoter mutations are very rare in urachal adenocarcinomas (unlike in UC) with differential diagnostic implications. Additionally, the low TERT promoter mutation rate in urachal adenocarcinomas is more comparable to colorectal adenocarcinomas than to UC, giving further support to recent genetic findings and therapeutic considerations.


Asunto(s)
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Regiones Promotoras Genéticas/genética , Telomerasa/genética , Neoplasias de la Vejiga Urinaria/genética , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neoplasias de la Vejiga Urinaria/patología
2.
Proc Natl Acad Sci U S A ; 105(17): 6403-8, 2008 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-18427119

RESUMEN

Signal processing in bacterial chemotaxis relies on large sensory complexes consisting of thousands of protein molecules. These clusters create a scaffold that increases the efficiency of pathway reactions and amplifies and integrates chemotactic signals. The cluster core in Escherichia coli comprises a ternary complex composed of receptors, kinase CheA, and adaptor protein CheW. All other chemotaxis proteins localize to clusters by binding either directly to receptors or to CheA. Here, we used fluorescence recovery after photobleaching (FRAP) to investigate the turnover of chemotaxis proteins at the cluster and their mobility in the cytoplasm. We found that cluster exchange kinetics were protein-specific and took place on several characteristic time scales that correspond to excitation, adaptation, and cell division, respectively. We further applied analytical and numerical data fitting to analyze intracellular protein diffusion and to estimate the rate constants of cluster equilibration in vivo. Our results indicate that the rates of protein turnover at the cluster have evolved to ensure optimal performance of the chemotaxis pathway.


Asunto(s)
Células Quimiorreceptoras/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Proteínas Bacterianas , Quimiotaxis , Difusión , Escherichia coli/citología , Recuperación de Fluorescencia tras Fotoblanqueo , Cinética , Unión Proteica , Transporte de Proteínas , Proteínas Recombinantes de Fusión/metabolismo
3.
Mol Microbiol ; 68(5): 1228-36, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18476921

RESUMEN

Chemoreceptors and cytoplasmic chemotaxis proteins in Escherichia coli form clusters that play a key role in signal processing. These clusters localize at cell poles and at specific positions along the cell body which correspond to future division sites, but the details of cluster formation and the mechanism of cluster distribution remain unclear. Here, we used fluorescence microscopy to investigate how the numbers and sizes of receptor clusters depend on the expression level of chemotaxis proteins and on the cell length. We show that the average cluster number saturates at high levels of protein expression at approximately 3.7 clusters per cell, well below the number of available positioning sites. Correspondingly, distances between clusters in filamentous cells saturate at an average of 1 mum but, even at saturating expression levels, individual cluster numbers and distances show a broad distribution around the mean. Our data imply a stochastic mode of cluster assembly, where a defined average interval between clusters along the cell body arises from competition between nucleation of new clusters and growth of existing clusters. Upon subsequent anchorage to defined lateral sites, clusters grow with rates that inversely depend on their size, and become polar upon several rounds of cell division.


Asunto(s)
Células Quimiorreceptoras/metabolismo , Quimiotaxis/fisiología , Escherichia coli/fisiología , Complejos Multiproteicos/fisiología , Receptores de Superficie Celular/fisiología , Transducción de Señal/fisiología , Proteínas Bacterianas , Escherichia coli/citología , Escherichia coli/crecimiento & desarrollo , Procesamiento de Imagen Asistido por Computador , Microscopía Fluorescente , Complejos Multiproteicos/metabolismo , Receptores de Superficie Celular/metabolismo
4.
EMBO J ; 26(6): 1615-23, 2007 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-17332753

RESUMEN

Chemotaxis receptors and associated signalling proteins in Escherichia coli form clusters that consist of thousands of molecules and are the largest native protein complexes described to date in bacteria. Clusters are located at the cell poles and laterally along the cell body, and play an important role in signal transduction. Much work has been done to study the structure and function of receptor clusters, but the significance of their positioning and the underlying mechanisms are not understood. Here, we used fluorescence imaging to study cluster distribution and follow cluster dynamics during cell growth. Our data show that lateral clusters localise to specific periodic positions along the cell body, which mark future division sites and are involved in the localisation of the replication machinery. The chemoreceptor cluster positioning is thus intricately related to the overall structure and division of an E. coli cell.


Asunto(s)
División Celular/fisiología , Quimiotaxis/fisiología , Escherichia coli/fisiología , Complejos Multiproteicos/fisiología , Receptores de Superficie Celular/fisiología , Transducción de Señal/fisiología , Escherichia coli/citología , Escherichia coli/metabolismo , Procesamiento de Imagen Asistido por Computador , Microscopía Fluorescente , Complejos Multiproteicos/metabolismo , Receptores de Superficie Celular/metabolismo
5.
Mol Microbiol ; 61(2): 407-17, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16856941

RESUMEN

Chemotactic stimuli in bacteria are sensed by large sensory complexes, or receptor clusters, that consist of tens of thousands of proteins. Receptor clusters appear to play a key role in signal processing, but their structure remains poorly understood. Here we used fluorescent protein fusions to study in vivo formation of the cluster core, which consists of receptors, a kinase CheA and an assisting protein CheW. We show that receptors aggregate through their cytoplasmic domains even in the absence of other chemotaxis proteins. Clustering is further enhanced by the binding of CheW. Surprisingly, we observed that some fragments of CheA bind receptor clusters well in the absence of CheW, although the latter does assist the binding of full-length CheA. The resulting mode of receptor cluster formation is consistent with an experimentally observed flexible stoichiometry of chemosensory complexes and with assumptions of recently proposed computer models of signal processing in chemotaxis.


Asunto(s)
Células Quimiorreceptoras/metabolismo , Escherichia coli/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Citoplasma/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Histidina Quinasa , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Quimiotácticas Aceptoras de Metilo , Metiltransferasas/genética , Complejos Multiproteicos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Transducción de Señal
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA