title: Characterization of the cytosolic tuberin-hamartin complex. Tuberin is a cytosolic chaperone for hamartin.
abstract: Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by a broad phenotypic spectrum that includes seizures, mental retardation, renal dysfunction and dermatological abnormalities. Mutations to either the TSC1 or TSC2 gene are responsible for the disease. The TSC1 gene encodes hamartin, a 130-kDa protein without significant homology to other known mammalian proteins. Analysis of the amino acid sequence of tuberin, the 200-kDa product of the TSC2 gene, identified a region with limited homology to GTPase-activating proteins. Previously, we demonstrated direct binding between tuberin and hamartin. Here we investigate this interaction in more detail. We show that the complex is predominantly cytosolic and may contain additional, as yet uncharacterized components alongside tuberin and hamartin. Furthermore, because oligomerization of the hamartin carboxyl-terminal coiled coil domain was inhibited by the presence of tuberin, we propose that tuberin acts as a chaperone, preventing hamartin self-aggregation.
authors.affiliation: Department of Clinical Genetics, Erasmus University, 3015 GE Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Nellist
authors.forename: M A
authors.initials: MA
authors.lastname: van Slegtenhorst
authors.forename: M
authors.initials: M
authors.lastname: Goedbloed
authors.forename: A M
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: D J
authors.initials: DJ
authors.lastname: Halley
authors.forename: P
authors.initials: P
authors.lastname: van der Sluijs
mesh_terms: D000818:Animals; D019556:COS Cells; D002850:Chromatography, Gel; D003600:Cytosol / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014402:Tuberous Sclerosis / Q000235:genetics; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor 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