Open AccessIdentification of F ‐box only protein 7 as a negative regulator of NF ‐kappa B signalling
Author(s) -
Kuiken Hendrik J.,
Egan David A.,
Laman Heike,
Bernards Rene,
Beijersbergen Roderick L.,
Dirac Annette M.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01524.x
Subject(s) - cullin , ubiquitin ligase , ubiquitin , f box protein , microbiology and biotechnology , ubiquitin conjugating enzyme , transcription factor , nuclear protein , nf κb , regulator , signal transduction , biology , nfkb1 , chemistry , biochemistry , gene
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 S kp, C ullin, 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 cIAP 1 and TRAF 2, resulting in decreased RIP 1 ubiquitination and lowered NF ‐ κB signalling activity.