title: The cellular response to ectopic overexpression of the tuberous sclerosis genes, TSC1 and TSC2: a proteomic approach.
abstract: The genes, TSC1 on chromosome 9q34, encoding hamartin, and TSC2 on chromosome 16p13.3, encoding tuberin, are responsible for tuberous sclerosis (TSC). TSC is an autosomal dominant tumor suppressor gene syndrome affecting about 1 in 6000 individuals. It is characterized by mental retardation and epilepsy. A variety of tumors characteristically occur in different organs of TSC patients and are believed to result from defects in cell cycle/cell size control. Hamartin and tuberin form a complex providing a tentative explanation for the similar disease phenotype in TSC patients with mutations in either of these genes. Beside overlap in many features of patients with TSC1 and TSC2 mutations, data accumulated providing evidence for specific clinical differences. In this study, we performed a proteomic approach of two-dimensional gel electrophoresis with subsequent mass spectrometrical identification of protein spots after ectopic overexpression of human TSC1 or TSC2. We found the protein levels of the calumenin precursor; the complement component 1; heterogeneous nuclear ribonucleoproteins, C1/C2; heterogeneous nuclear ribonucleoprotein, C1-like protein; nascent polypeptide-associated complex-alpha; proteasome subunit alpha type 5; reticulocalbin 1 precursor; translationally-controlled tumor protein; UV excision repair protein, RAD23 homolog B; elongation factor 1-delta; and the eukaryotic initiation factors, eIF-4A-like NUK-34 and eIF-6; to be deregulated upon ectopic TSC gene expression. These findings suggest that deregulation of the control of these new target proteins might contribute to the development of tubers/hamartomas in tuberous sclerosis patients. The data are presented and discussed in the context of the published literature on proteomic approaches for the identification of targets of the TSC genes.
authors.affiliation: Medical Genetics, Department of Obstetrics and Gynecology, Medical University of Vienna, A-1090 Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
authors.forename: Margit
authors.initials: M
authors.lastname: Rosner
authors.forename: Michael
authors.initials: M
authors.lastname: Fountoulakis
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D020543:Proteome; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins