title: Analysis of TSC1 truncations defines regions involved in TSC1 stability, aggregation and interaction.
abstract: Tuberous 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, interact to form a protein complex that inhibits signal transduction to the downstream effectors of the target of rapamycin complex 1 (TORC1). Here we investigate TSC1 structure and function by analysing a series of truncated TSC1 proteins. We identify specific regions of the protein that are important for TSC1 stability, localisation, interactions and function.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
authors.forename: Marianne
authors.initials: M
authors.lastname: Hoogeveen-Westerveld
authors.forename: Carla
authors.initials: C
authors.lastname: Exalto
authors.forename: Anneke
authors.initials: A
authors.lastname: Maat-Kievit
authors.forename: Ans
authors.initials: A
authors.lastname: van den Ouweland
authors.forename: Dicky
authors.initials: D
authors.lastname: Halley
authors.forename: Mark
authors.initials: M
authors.lastname: Nellist
mesh_terms: D002478:Cells, Cultured; D017353:Gene Deletion; D042822:Genomic Instability; D006801:Humans; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D025941:Protein Interaction Mapping; D055503:Protein Multimerization / Q000235:genetics*; D055550:Protein Stability; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D013329:Structure-Activity Relationship; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins