Identification of F‐box only protein 7 as a negative regulator of NF‐kappaB signalling

The nuclear factor κB (NF‐κB) signalling 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 tran...

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Vydané v:	Journal of cellular and molecular medicine Ročník 16; číslo 9; s. 2140 - 2149
Hlavní autori:	Kuiken, Hendrik J., Egan, David A., Laman, Heike, Bernards, Rene, Beijersbergen, Roderick L., Dirac, Annette M.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	England John Wiley & Sons, Inc 01.09.2012 Blackwell Publishing Ltd
Predmet:	Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism cIAP1 F-Box Proteins - genetics F-Box Proteins - metabolism FBXO7 Gene Expression Regulation HEK293 Cells Humans Immunoblotting Immunoprecipitation Inhibitor of Apoptosis Proteins - genetics Inhibitor of Apoptosis Proteins - metabolism NF-kappa B - genetics NF-kappa B - metabolism NF‐κB signalling Nuclear Pore Complex Proteins - genetics Nuclear Pore Complex Proteins - metabolism Original regulatory ubiquitination RNA interference RNA, Small Interfering - genetics RNA, Small Interfering - metabolism RNA-Binding Proteins - genetics RNA-Binding Proteins - metabolism Signal Transduction siRNA Tumor Necrosis Factor-alpha - genetics Tumor Necrosis Factor-alpha - metabolism Ubiquitination
ISSN:	1582-1838, 1582-4934, 1582-4934
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Popis
Shrnutí:	The nuclear factor κB (NF‐κB) signalling 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, we screened a synthetic siRNA library targeting enzymes involved in ubiquitin conjugation and de‐conjugation for modifiers of regulatory ubiquitination events in NF‐κB signalling. We identified F‐box protein only 7 (FBXO7), a component of Skp, Cullin, F‐box (SCF)‐ubiquitin ligase complexes, as a negative regulator of NF‐κB signalling. F‐box protein only 7 binds to, and mediates ubiquitin conjugation to cIAP1 and TRAF2, resulting in decreased RIP1 ubiquitination and lowered NF‐κB signalling activity.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1582-1838 1582-4934 1582-4934
DOI:	10.1111/j.1582-4934.2012.01524.x