Article
Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function.
Cell - 24 Apr 2014
Papa Antonella, Wan Lixin, Bonora Massimo, Salmena Leonardo, Song Min Sup, Hobbs Robin M, Lunardi Andrea, Webster Kaitlyn, Ng Christopher, Newton Ryan H, Knoblauch Nicholas, Guarnerio Jlenia, Ito Keisuke, Turka Laurence A, Beck Andy H, Pinton Paolo, Bronson Roderick T, Wei Wenyi, Pandolfi Pier Paolo
Abstract excerpt
PTEN dysfunction plays a crucial role in the pathogenesis of hereditary and sporadic cancers. Here, we show that PTEN homodimerizes and, in this active conformation, exerts lipid phosphatase activity on PtdIns(3,4,5)P3. We demonstrate that catalytically inactive cancer-associated PTEN mutants heterodimerize with wild-type PTEN and constrain its phosphatase activity in a dominant-negative manner. To study the...
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