The p105 NF-?B precursor is a pseudo substrate of the ubiquitin ligase FBXO7, and its binding to the ligase stabilizes it and results in stimulated cell proliferation

The NF-?B transcription factor is involved in inflammation and cell proliferation, survival, transformation. It a heterodimer made of p50 or p52 member the Rel family proteins. are derived from limited ubiquitin- proteasome-mediated proteolytic processing larger precursors p105 p100, respectively. Both can be either processed completely degraded by ubiquitin-proteasome system. Previous work our laboratory identified KPC1 as ubiquitin ligase that mediates to subunit. Overexpression leads increased level with resultant marked tumor-suppressive effect. In present study, we identify FBXO7, known binds ubiquitinates it, but surprisingly, its accumulation p65 - partner proliferation. Importantly, ?F-Box mutant FBXO7 which inactive has similar effects on strongly suggesting pseudo substrate FBXO7.