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

Ronald G. Udasin, Yossi Gottfried, Bertrand Fabre, Beatrice Bercovich, Tamar Ziv, Aaron Ciechanover

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)224-230
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume558
DOIs
StatePublished - 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

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