A melhor ferramenta para a sua pesquisa, trabalho e TCC!
Página 1 dos resultados de 4394 itens digitais encontrados em 0.007 segundos
- LIPPINCOTT WILLIAMS & WILKINS
- The National Academy of Sciences
- The American Society of Human Genetics
- American Society for Investigative Pathology
- American Society of Human Genetics
- Oxford University Press
- Public Library of Science
- Landes Bioscience
- Oxford Univ Press
- Universidade de Tubinga
- NATURE PUBLISHING GROUP; NEW YORK
- Blackwell Publishing Ltd
- Mais Publicadores...
Resultados filtrados por Publicador: Oxford Univ Press
‣ ARX homeodomain mutations abolish DNA binding and lead to a loss of transcriptional repression
Fonte: Oxford Univ Press
Publicador: Oxford Univ Press
Tipo: Artigo de Revista Científica
Publicado em //2012
Português
Relevância na Pesquisa
499.24277%
#Humans#Cell Nucleus#Transcription Factors#Repressor Proteins#DNA#DNA-Binding Proteins#Homeodomain Proteins#Protein Structure, Tertiary#Active Transport, Cell Nucleus#Mutation, Missense#Transcription, Genetic
Mutations in the Aristaless-related homeobox (ARX) gene are one of the most frequent causes of X-linked intellectual disability (ID). Several missense mutations, clustered in the paired-type homeodomain of ARX, have been identified. These mutations lead to a range of phenotypes from X-linked lissencephaly with abnormal genitalia to seizure disorders without brain malformations including X-linked infantile spasms with ID (ISSX-ID) and X-linked myoclonic epilepsy with spasticity and ID (XMESID). The effect of these mutations on the DNA-binding and transcriptional activity has been evaluated. Luciferase reporter assays showed altered repression activity of ARX by all mutations, causing brain malformations and ISSX-ID phenotypes, but not by the P353L mutation implicated in a milder phenotype of XMESID. Similarly, transient overexpression of wild-type ARX repressed endogenous expression of known ARX targets, LMO1 and SHOX2, when measured by real-time quantitative polymerase chain reaction. Overall, the molecular consequence of missense mutations correlated well with the severity of the clinical phenotype. In all mutations tested, except P353L, the DNA binding was abolished. Electrophoretic mobility shift assay results were validated using chromatin immunoprecipitation following overexpression of normal and selected missense mutations. Unlike wild-type ARX and clinically less severe mutations...
Link permanente para citações: