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