Shen RR, Zhou AY, Kim E, Lim E, Habelhah H, Hahn WC

NF-κB transcription factors are central regulators of inflammation and when dysregulated contribute to malignant transformation. IκB kinase ε (IKKε, IKKi, IKBKE) is a breast oncogene that is amplified in 30% of breast cancers and drives transformation in a NF-κB-dependent manner. Here we demonstrate that IKKε interacts with and phosphorylates TRAF2 ...

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at Ser11 in vitro and in vivo. This activity promotes Lys63-linked TRAF2 ubiquitination, NF-κB activation and is essential for IKKε-transformation. Breast cancer cells that depend on IKKε expression for survival are also dependent on TRAF2. This work defines TRAF2 phosphorylation as one key effector of IKKε-induced mammary epithelial cell transformation.

Date: Sep. 24, 2012

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