Abstract
The NF-κB transcription factor is involved in inflammation and cell proliferation, survival, and transformation. It is a heterodimer made of p50 or p52 and a member of the Rel family of proteins. p50 and p52 are derived from limited ubiquitin- and proteasome-mediated proteolytic processing of the larger precursors p105 and p100, respectively. Both precursors can be either processed or completely degraded by the ubiquitin-proteasome system. Previous work in our laboratory identified KPC1 as a ubiquitin ligase that mediates processing of p105 to the p50 subunit. Overexpression of the ligase leads to increased level of p50 with a resultant marked tumor-suppressive effect. In the present study, we identify FBXO7, a known ubiquitin ligase that binds to p105 and ubiquitinates it, but surprisingly, leads to its accumulation and to that of p65 - the Rel partner of p50 - and to increased cell proliferation. Importantly, a ΔF-Box mutant of FBXO7 which is inactive has similar effects on accumulation of p105 and cell proliferation, strongly suggesting that p105 is a pseudo substrate of FBXO7.
Original language | English |
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Pages (from-to) | 224-230 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 558 |
DOIs | |
State | Published - 18 Jun 2021 |
Keywords
- FBXO7
- NF-kB
- NF-κB
- Protein degradation
- Ubiquitin-proteasome system
- p105
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Biophysics
- Biochemistry
- Cell Biology