Identification of a region required for TSC1 stability by functional analysis of TSC1missense mutations found in individuals with tuberous sclerosis complexReportar como inadecuado




Identification of a region required for TSC1 stability by functional analysis of TSC1missense mutations found in individuals with tuberous sclerosis complex - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Medical Genetics

, 10:88

First Online: 11 September 2009Received: 09 March 2009Accepted: 11 September 2009

Abstract

BackgroundTuberous sclerosis complex TSC is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34, or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin mTOR. Recently it has been shown that missense mutations to the TSC1 gene can cause TSC.

MethodsWe have used in vitro biochemical assays to investigate the effects on TSC1 function of TSC1 missense variants submitted to the Leiden Open Variation Database.

ResultsWe identified specific substitutions between amino acids 50 and 190 in the N-terminal region of TSC1 that result in reduced steady state levels of the protein and lead to increased mTOR signalling.

ConclusionOur results suggest that amino acid residues within the N-terminal region of TSC1 are important for TSC1 function and for maintaining the activity of the TSC1-TSC2 complex.

AbbreviationsTSCtuberous sclerosis complex

GAPGTPase activating protein

mTORmammalian target of rapamycin

S6Kp70 S6 kinase.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-10-88 contains supplementary material, which is available to authorized users.

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Autor: Melika Mozaffari - Marianne Hoogeveen-Westerveld - David Kwiatkowski - Julian Sampson - Rosemary Ekong - Sue Povey - Johan 

Fuente: https://link.springer.com/



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