Tuberous sclerosis gene products in proliferation control

• Published in: Mutation Research-Reviews in Mutation Research Vol. 488; no. 3; pp. 233 - 239
• Main Authors: Hengstschläger, Markus, Rodman, David M, Miloloza, Angelina, Hengstschläger-Ottnad, Elke, Rosner, Margit, Kubista, Marion
• Format: Book Review Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01.07.2001; Amsterdam Elsevier Science; New York, NY
• Subjects: Active Transport, Cell Nucleus; Animals; Biological and medical sciences; Carcinoma, Renal Cell - genetics; Cell Compartmentation; Cell cycle; Cell Cycle - genetics; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Cycle Proteins - physiology; Cell Division - genetics; Cell physiology; Cell Size - genetics; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosomes, Human, Pair 16 - genetics; Chromosomes, Human, Pair 9 - genetics; Cyclin-Dependent Kinase Inhibitor p27; Drosophila; Drosophila melanogaster - cytology; Drosophila melanogaster - genetics; Drosophila Proteins; Fundamental and applied biological sciences. Psychology; Genes, Dominant; Genes, Tumor Suppressor; hamartin; hamartoma; Hamartoma - genetics; Humans; Insect Proteins - genetics; Insect Proteins - physiology; Kidney Neoplasms - genetics; Loss of Heterozygosity; Macromolecular Substances; Medical sciences; Molecular and cellular biology; Neurology; Proliferation; Proteins - genetics; Proteins - physiology; Rats; Rats, Mutant Strains; Repressor Proteins - genetics; Repressor Proteins - physiology; TSC1; TSC1 gene; TSC2; TSC2 gene; tuberin; Tuberous sclerosis; Tuberous Sclerosis - genetics; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins; Tumors of the nervous system. Phacomatoses; Tuberous sclerosis; TSC2; TSC1; Proliferation; Cell cycle; Human; Cell proliferation; Nervous system diseases; Loss of heterozygosity; Tumor; Review; Mutation; Bourneville syndrome; Genetic disease; Tumor suppressor gene
• ISSN: 1383-5742; 0027-5107; 1388-2139
• DOI: 10.1016/S1383-5742(01)00058-8

Two genes, TSC1 and TSC2, have been shown to be responsible for tuberous sclerosis (TSC). The detection of loss of heterozygosity of TSC1 or TSC2 in hamartomas, the growths characteristically occurring in TSC patients, suggested a tumor suppressor function for their gene products hamartin and tuberin. 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 studying the effects of deregulated TSC1 expression. Elucidation of the cellular functions of these proteins will form the basis of a better understanding of how mutations in these genes cause the disease and for the development of new therapeutic strategies.