Tuberous sclerosis gene products in proliferation control.
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.
Hengstschläger
M
M
Obstetrics and Gynecology, Prenatal Diagnosis and Therapy, University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria. markus.hengstschlaeger@akh-wien.ac.at
Rodman
D M
DM
Miloloza
A
A
Hengstschläger-Ottnad
E
E
Rosner
M
M
Kubista
M
M
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics; D002451:Cell Compartmentation; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000235:genetics*; D048429:Cell Size / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics; D005799:Genes, Dominant; D016147:Genes, Tumor Suppressor; D006222:Hamartoma / Q000235:genetics; D006801:Humans; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D007680:Kidney Neoplasms / Q000235:genetics; D019656:Loss of Heterozygosity; D046911:Macromolecular Substances; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D046911:Macromolecular Substances; D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; C000624651:Tsc1 protein, mouse; C000624652:Tsc1 protein, rat; C000624654:Tsc2 protein, mouse; C000624655:Tsc2 protein, rat; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C117726:gig protein, Drosophila; D050760:Cyclin-Dependent Kinase Inhibitor p27