Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations to the TSC1 and TSC2 tumour suppressor genes. We detected two sequence changes involving the TSC2 stop codon and investigated the effects of these changes on the expression of tuberin, the TSC2 gene product, and on the binding between tuberin and the TSC1 gene product, hamartin. While elongation of the tuberin open reading frame by 17 amino acids did not interfere with tuberin-hamartin binding, a longer extension prevented this interaction. Our data illustrate how functional protein assays can assist in the verification and characterisation of disease-causing mutations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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COS Cells
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Codon, Terminator / genetics*
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Family Health
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Female
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Genetic Variation
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Humans
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Male
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Mutation
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Pedigree
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Protein Binding
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Proteins / genetics
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Proteins / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Tuberous Sclerosis / genetics*
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Tuberous Sclerosis / pathology
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Tuberous Sclerosis Complex 1 Protein
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins
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Two-Hybrid System Techniques
Substances
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Codon, Terminator
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Proteins
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Repressor Proteins
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TSC1 protein, human
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TSC2 protein, human
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Tuberous Sclerosis Complex 1 Protein
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins