WWP1 Gain-of-Function Inactivation of PTEN in Cancer Predisposition
Yu-Ru Lee, Lamis Yehia, Takahiro Kishikawa, Ying Ni, Brandie Heald, Jinfang Zhang, Nivedita Panch, Jing Liu, Wenyi Wei, Charis Eng, Pier Paolo Pandolfi
Abstract
BACKGROUND: mutations. In a previous study, we found that the E3 ubiquitin ligase WWP1 negatively regulates the function of PTEN. METHODS: variants. RESULTS: variants resulted in gain-of-function effects, which led to aberrant enzymatic activation with consequent PTEN inactivation, thereby triggering hyperactive growth-promoting PI3K signaling in cellular and murine models. CONCLUSIONS: as a cancer-susceptibility gene through direct aberrant regulation of the PTEN-PI3K signaling axis. (Funded by the National Institutes of Health and others.).
Topics & Concepts
PTENCancerGenetic predispositionGain of functionFunction (biology)Cancer researchBiologyChemistryGeneticsMutationGenePI3K/AKT/mTOR pathwayApoptosisPI3K/AKT/mTOR signaling in cancerUbiquitin and proteasome pathwaysProtein Tyrosine Phosphatases