title: Protein levels of alpha1-tubulin, protein disulfide isomerase, tropomyosins and vimentin are regulated by the tuberous sclerosis gene products.
abstract: Tuberous sclerosis (TSC) is an autosomal dominant tumour suppressor gene syndrome affecting about 1 in 6000 individuals. It is characterized by mental retardation and epilepsy. A variety of tumours characteristically occur in different organs of TSC patients. Typically, highly epileptogenic dysplastic lesions (tubers) composed of abnormal shaped neurones can be detected in the cerebral cortex. Two tumour suppressor genes have been shown to be responsible for this disease: TSC1, encoding hamartin, and TSC2, encoding tuberin. 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 alpha1-tubulin, protein disulfide isomerase, tropomyosin 3 and 5 and vimentin to be regulated by the two tuberous sclerosis gene products. The here presented findings suggest that deregulation of the control of these target proteins might contribute to the development of tumours in tuberous sclerosis patients. These data provide important new insights into the molecular development of this disease especially since alpha1-tubulin, protein disulfide isomerase and certain tropomyosins have also been implicated in the regulation of neuronal differentiation.
authors.affiliation: Obstetrics and Gynecology, University of Vienna, Prenatal Diagnosis and Therapy, Währinger Gürtel 18-20, 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: Ji-Eun
authors.initials: JE
authors.lastname: Oh
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D015153:Blotting, Western; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D019704:Protein Disulfide-Isomerases / Q000032:analysis* / Q000096:biosynthesis / Q000494:pharmacology; D040901:Proteomics; D014335:Tropomyosin / Q000032:analysis* / Q000096:biosynthesis / Q000494:pharmacology; D014402:Tuberous Sclerosis / Q000150:complications* / Q000235:genetics*; D014404:Tubulin / Q000032:analysis* / Q000096:biosynthesis / Q000494:pharmacology; D014746:Vimentin / Q000032:analysis* / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: D014335:Tropomyosin; D014404:Tubulin; D014746:Vimentin; D019704:Protein Disulfide-Isomerases