Kuiken HJ, Egan DA, Laman H, Bernards R, Beijersbergen RL, Dirac AM

The Nuclear factor κB (NF-κB) signaling pathway controls important cellular events such as cell proliferation, differentiation, apoptosis and immune responses. Pathway activation occurs rapidly upon TNFα stimulation and is highly dependent on ubiquitination events. Using cytoplasmic to nuclear translocation of the NF-κB transcription factor family member p65 as a read-out, ...

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we screened a synthetic siRNA library targeting enzymes involved in ubiquitin conjugation and de-conjugation for modifiers of regulatory ubiquitination events in NF-κB signaling. We identified F-Box protein only 7 (FBXO7), a component of SCF-ubiquitin ligase complexes, as a negative regulator of NF-κB signaling. FBXO7 binds to, and mediates ubiquitin conjugation to cIAP1 and TRAF2, resulting in decreased RIP1 ubiquitination and lowered NF-κB signaling activity. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Date: Jan. 02, 2012

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