1) La descarga del recurso depende de la página de origen
2) Para poder descargar el recurso, es necesario ser usuario registrado en Universia


Opción 1: Descargar recurso

Detalles del recurso

Descripción

We report that the dominant human missense mutations G303E and G296S in GATA4, a cardiac-specific transcription factor gene, cause atrioventricular septal defects and valve abnormalities by disrupting a signaling cascade involved in endocardial cushion development. These GATA4 missense mutations, but not a mutation causing secundum atrial septal defects (S52F), demonstrated impaired protein interactions with SMAD4, a transcription factor required for canonical bone morphogenetic protein/transforming growth factor-β (BMP/TGF-β) signaling. Gata4 and Smad4 genetically interact in vivo: atrioventricular septal defects result from endothelial-specific Gata4 and Smad4 compound haploinsufficiency. Endothelial-specific knockout of Smad4 caused an absence of valve-forming activity: Smad4-deficient endocardium was associated with acellular endocardial cushions, absent epithelial-to-mesenchymal transformation, reduced endocardial proliferation, and loss of Id2 expression in valve-forming regions. We show that Gata4 and Smad4 cooperatively activated the Id2 promoter, that human GATA4 mutations abrogated this activity, and that Id2 deficiency in mice could cause atrioventricular septal defects. We suggest that one determinant of the phenotypic spectrum caused by human GATA4 mutations is differential effects on GATA4/SMAD4 interactions required for endocardial cushion development.

Pertenece a

PubMed Central (PMC3 - NLM DTD)  

Autor(es)

Moskowitz, Ivan P. -  Wang, Jun -  Peterson, Michael A. -  Pu, William T. -  Mackinnon, Alexander C. -  Oxburgh, Leif -  Chu, Gerald C. -  Sarkar, Molly -  Berul, Charles -  Smoot, Leslie -  Robertson, Elizabeth J. -  Schwartz, Robert -  Seidman, Jonathan G. -  Seidman, Christine E. - 

Id.: 54459972

Idioma: inglés  - 

Versión: 1.0

Estado: Final

Palabras claveBiological Sciences - 

Tipo de recurso: Text  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

Requerimientos técnicos:  Browser: Any - 

Fecha de contribución: 09-sep-2011

Contacto:

Localización:

Otros recursos de la misma colección

  1. The precise temporal calibration of dinosaur origins Many hypotheses have been put forth to explain the origin and early radiation of dinosaurs, but poor...
  2. Calcium-dependent oligomerization of CAR proteins at cell membrane modulates ABA signaling Drought and salinity are the major threats to crop productivity at a worldwide scale. A fundamental ...
  3. Bioengineered yeast-derived vacuoles with enhanced tissue-penetrating ability for targeted cancer therapy Tumor tissues have formidable physiological barriers, such as a high interstitial pressure and a den...
  4. Driven to metastasize: Kinases as potential therapeutic targets in prostate cancer
  5. Small fluorescence-activating and absorption-shifting tag for tunable protein imaging in vivo We developed a small protein tag enabling fluorescent labeling of proteins in living cells and in mu...

Aviso de cookies: Usamos cookies propias y de terceros para mejorar nuestros servicios, para análisis estadístico y para mostrarle publicidad. Si continua navegando consideramos que acepta su uso en los términos establecidos en la Política de cookies.