TSC1 and TSC2: genes that are mutated in the human genetic disorder tuberous sclerosis

Abstract

The tuberous sclerosis complex genes TSC1 and TSC2 were first identified by positional cloning strategies in the heritable human disorder tuberous sclerosis. They encode previously unknown proteins, termed hamartin and tuberin respectively, that form a functional complex. The phenotypic manifestations of tuberous sclerosis are extremely diverse and suggest normal roles for TSC1 and TSC2 in regulating the growth, proliferation, migration and differentiation of many cell types. Investigations of TSC1 and TSC2 in a number of model organisms and cell-culture systems have provided new insights into the mechanisms through which these roles are effected. Most promisingly, the hamartin–tuberin complex has been shown to function as a negtive regulator of the insulin receptor/phosphoinositide 3-kinase/S6 kinase pathway. Drugs that act to inhibit this pathway may have therapeutic potential for tuberous sclerosis and the related disorder lymphangioleiomyomatosis.