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Cell Cycle. 2011 Sep 15;10(18):3129-39. Epub 2011 Sep 15.

The tumor suppressor tuberin regulates mitotic onset through the cellular localization of cyclin B1.

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1
Department of Biological Sciences, University of Windsor, Windsor, ON, Canada.

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.

PMID:
21900748
DOI:
10.4161/cc.10.18.17296
[Indexed for MEDLINE]
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