Linked Life Data

11741833

Source:http://linkedlifedata.com/resource/pubmed/id/11741833

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2001-12-19
pubmed:abstractText
Critical functions of hamartin and tuberin, encoded by the TSC1 and TSC2 genes, are likely to be closely linked. The proteins interact directly with one another and mutations affecting either gene result in the tuberous sclerosis phenotype. However, the regions of hamartin and tuberin that interact have not been well defined, and the relationship between their interaction and the pathogenesis of tuberous sclerosis has not been explored. To address these issues a series of hamartin and tuberin constructs were used to assay for interaction in the yeast two-hybrid system. Hamartin (amino acids 302-430) and tuberin (amino acids 1-418) interacted strongly with one another. A region of tuberin encoding a putative coiled-coil (amino acids 346-371) was necessary but not sufficient to mediate the interaction with hamartin, as more N-terminal residues were also required. A region of hamartin (amino acids 719-998) predicted to encode coiled-coils was capable of oligermerization but was not important for the interaction with tuberin. Subtle, non-truncating mutations identified in patients with tuberous sclerosis and located within the putative binding regions of hamartin (N198_F199delinsI;593-595delACT) or tuberin (G294E and I365del), abolished or dramatically reduced interaction of the proteins as assessed by yeast two-hybrid assays and by co-immunoprecipitation of the full-length proteins from Cos7 cells. In contrast, three non-pathogenic missense polymorphisms of tuberin (R261W, M286V, R367Q) in the same region as the disease-causing TSC2 mutations did not. These results indicate a requirement for interaction in critical growth suppressing functions of hamartin and tuberin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2899-905
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11741833-Animals, pubmed-meshheading:11741833-Binding Sites, pubmed-meshheading:11741833-COS Cells, pubmed-meshheading:11741833-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:11741833-Gene Deletion, pubmed-meshheading:11741833-Genes, Tumor Suppressor, pubmed-meshheading:11741833-Humans, pubmed-meshheading:11741833-Immunoblotting, pubmed-meshheading:11741833-Immunoenzyme Techniques, pubmed-meshheading:11741833-Lymphocyte Activation, pubmed-meshheading:11741833-Molecular Chaperones, pubmed-meshheading:11741833-Mutagenesis, Site-Directed, pubmed-meshheading:11741833-Mutation, pubmed-meshheading:11741833-Phosphorylation, pubmed-meshheading:11741833-Plasmids, pubmed-meshheading:11741833-Protein Binding, pubmed-meshheading:11741833-Proteins, pubmed-meshheading:11741833-Repressor Proteins, pubmed-meshheading:11741833-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11741833-Transfection, pubmed-meshheading:11741833-Tuberous Sclerosis, pubmed-meshheading:11741833-Tumor Suppressor Proteins, pubmed-meshheading:11741833-Two-Hybrid System Techniques
pubmed:year
2001
pubmed:articleTitle
Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin.
pubmed:affiliation
Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK. hodgesak@cardiff.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't