INTERACTION BETWEEN HAMARTIN AND TUBERIN, THE TSC1 AND TSC2 GENE-PRODUCTS

Tuberous sclerosis (TSC) is an autosomal dominant disorder caused by a mutation in either the TSC1 or TSC2 tumour suppressor gene. The disea se is characterized by a broad phenotypic spectrum that can include se izures, mental retardation, renal dysfunction and dermatological abnor malities, TSC2 encodes tuberin, a putative GTPase activating protein f or rap1 and rab5. The TSC1 gene was recently identified and codes for hamartin, a novel protein with no significant homology to tuberin or a ny other known vertebrate protein. Here, we show that hamartin and tub erin associate physically in vivo and that the interaction is mediated by predicted coiled-coil domains. Our data suggest that hamartin and tuberin function in the same complex rather than in separate pathways.