Tuberous sclerosis gene products in proliferation control

Two genes, TSC1 and TSC2, have been shown to be responsible for tuberous sc lerosis (TSC). The detection of loss of heterozygosity of TSC1 or TSC2 in h amartomas, the growths characteristically occurring in TSC patients, sugges ted a tumor suppressor function for their gene products hamartin and tuberi n. Studies analyzing ectopically modulated expression of TSC2 in human and rodent cells together with the finding that a homolog of TSC2 regulates the Drosophila cell cycle suggest that TSC is a disease of proliferation/cell cycle control. We discuss this question including very recent data obtained from analyzing mice expressing a modulated TSC2 transgene, and from studyi ng the effects of deregulated TSC1 expression. Elucidation of the cellular functions of these proteins will form the basis of a better understanding o f how mutations in these genes cause the disease and for the development of new therapeutic strategies. (C) 2001 Elsevier Science B.V. All rights rese rved.