The TSC1 gene product, hamartin, negatively regulates cell proliferation

Tuberous sclerosis is an autosomal dominant hereditary disease caused by mu tations in either the TSC1 or the TSC2 tumor suppressor gene. The TSC1 gene on chromosome 9q34 encodes a 130 kDa protein named hamartin, and the TSC2 gene on chromosome 16p13.3 codes for tuberin, a 200 kDa protein. Here we sh ow that expression of hamartin, assayed by immunoblot analyses, is high in G(0)-arrested cells and hamartin is expressed throughout the entire ongoing cell cycle. An interaction of hamartin and tuberin can be detected in ever y phase of the cell cycle. Ectopic expression of high levels of hamartin at tenuates cellular proliferation. We provide evidence that this effect could depend on a coiled-coil region earlier proposed to be involved in binding of hamartin to tuberin, Further investigations revealed that hamartin affec ts cell proliferation via deregulation of G(1) phase, Our data have a clear impact on understanding the role of hamartin during development of this di sease.