Oncogenic Ras-Induced Expression of Noxa and Beclin-1 Promotes Autophagic Cell Death and Limits Clonogenic Survival
作者： Mohamed Elgendy , Clare Sheridan , Gabriela Brumatti , Seamus J. Martin
DOI: 10.1016/J.MOLCEL.2011.02.009
关键词:
摘要: Deregulated oncogenes such as MYC and RAS are typically insufficient to transform cells on their own due the activation of pathways that restrain proliferation. Previous studies have shown oncogenic H-Ras can induce proliferative arrest or senescence, depending cellular context. Here, we show deregulated activity also lead caspase-independent cell death with features autophagy. Ras-induced autophagy was associated upregulation BH3-only protein Noxa well regulator Beclin-1. Silencing Beclin-1 expression reduced increased clonogenic survival. inhibited by coexpression Bcl-2 family members inhibit function. Noxa-mediated displacement member, Mcl-1, from Thus, promotes autophagic death, which represents a mechanism limit potential Ras signals.
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