title: The tumor suppressor tuberin regulates mitotic onset through the cellular localization of cyclin B1.
abstract: Tuberous sclerosis is a multi-organ disorder characterized by the formation of benign tumors, called hamartomas, which affects more than 1 million people worldwide. The syndrome is initiated by a mutation in one of two tumor suppressor genes, TSC1 or TSC2, that encode for the proteins hamartin and tuberin, respectively. Herein, we demonstrate that tuberin binds and regulates the G 2/M cyclin, cyclin B1. We have determined that this binding region encompasses a mutational hotspot within tuberin that is implicated in some of the most severe cases of TS. Mimicking a mutation found in a subset of patients with tuberous sclerosis, we found a significant reduction in the binding between tuberin and cyclin B1. Functionally, our data supports that tuberin plays a role in regulating the cellular localization of cyclin B1. These results demonstrate a novel and clinically relevant mechanism, where tuberin functions in mitotic onset.
authors: Department of Biological Sciences, University of Windsor, Windsor, ON, Canada.
authors: Elizabeth
authors: E
authors: Fidalgo da Silva
authors: Shora B
authors: SB
authors: Ansari
authors: Jiamila
authors: J
authors: Maimaiti
authors: Elizabeth A
authors: EA
authors: Barnes
authors: Monica
authors: M
authors: Kong-Beltran
authors: Daniel J
authors: DJ
authors: Donoghue
authors: Lisa A
authors: LA
authors: Porter
mesh_terms: D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D051379:Mice; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D041681:NIH 3T3 Cells; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014402:Tuberous Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D011993:Recombinant Fusion Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; C000624651:Tsc1 protein, mouse; C000624654:Tsc2 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins