title: Hamartin and tuberin: working together for tumour suppression.
abstract: TSC1 and TSC2 are two recently identified tumour suppressor genes encoding hamartin and tuberin, respectively, and involved in pathogenesis of tuberous sclerosis, neurological disorder connected with the development of hamartomas in numerous organ systems, including the brain, kidneys, heart and liver. Both protein products of TSC1 and TSC2 form an intracellular complex exerting GTPase-activating (GAP) activity towards a small G protein, Ras homologue enriched in brain (Rheb). Inhibition of Rheb is important for the regulation of mTOR pathway, while mutation of hamartin or tuberin results in uncontrolled cell cycle progression. Tuberin, possessing the Rheb-GAP domain, is phosphorylated by several kinases that confer the signals of growth factor stimulation or low cellular energy levels. Such a modification of tuberin influences its activity within the complex with hamartin and positively or negatively modulates mTOR-regulated protein translation and cellular proliferation. Current article describes biochemical properties of hamartin and tuberin, their known regulatory phosphorylation sites and binding partners.
authors.affiliation: Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Warsaw, Poland. jjozwiak@atdv.com.pl
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Jozwiak
mesh_terms: D002471:Cell Transformation, Neoplastic; D006133:Growth Substances / Q000096:biosynthesis; D006222:Hamartoma / Q000503:physiopathology*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D000076205:Ras Homolog Enriched in Brain Protein; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D006133:Growth Substances; D009479:Neuropeptides; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D010770:Phosphotransferases; D020559:Monomeric GTP-Binding Proteins