Title

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

Document Type

Article

Publication Date

2011

Publication Title

CELL CYCLE

Volume

10

Issue

18

First Page

3129

Last Page

3139

DOI

10.4161/cc.10.18.17296

Keywords

cell cycle, TSC2, Cdk1, hamartin, hamartoma, cancer

Abstract

Tuberous sclerosis is a multi-organ disorder characterized by the formation of benign tumors, called hamartomas, which affect more than 1 million people worldwide. The syndrome is initiated by a mutation in one of two tumor suppressor genes, TSC1 or TSC2 which 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 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.