Role of the ubiquitin ligase KPC1 in NF-kappa B activation and tumor suppression

Yelena Kravtsova-Ivantsiv, Yong Tae Kwon, Aaron Ciechanover

Research output: Contribution to journalReview articlepeer-review


The nuclear factor-kappa B (NF-κB) transcription factor plays an essential role in the host immune response to different pathogens and genotoxic stimuli. In addition and either dependently or independently, it also promotes malignant transformation. The first step in its activation is conversion of extracellular stimuli to a cascade of reactions mediated by a variety of membrane receptors. The activated receptor transmits the signal through downstream proteins to activate different kinases. Subsequently, the inhibitory proteins that sequester NF-κB in the cytoplasm are phosphorylated, ubiquitinated, and degraded in the proteasome. Free NF-κB then enters the nucleus to initiate its transcriptional program. An important signaling “code” in the multiple-step NF-κB activating cascade consists of different ubiquitin (Ub) chains that are assembled on the different effector proteins through different lysine residues in the Ub molecule. Together with this unique set of proteins in the cascade, Ub chains form the platform for the binding of downstream interacting partners. One unknown link in the activation of NF-κB was the ubiquitin ligase that catalyzes generation of the active p50 subunit from its p105 inactive precursor. We found that KPC1 ubiquitinates p105 and catalyzes its processing to p50 under both basal and signal-induced conditions. A variety of biological functions carried out by NF-κB, depends on the dimeric composition of the transcription factor, and can determine the tumor suppression/promotion fate of the cell. Overexpression of KPC1 probably shifts the balance between NF-κB subunits from the “canonical” p50·p65 heterodimer to a p50 homodimer which results in a strong tumor suppressive phenotype.

Original languageEnglish
Article number8
JournalJournal of Analytical Science and Technology
Issue number1
StatePublished - 1 Dec 2016


  • 26S proteasome
  • KPC1
  • NF-kappa B
  • Tumor development
  • Ubiquitin
  • p105

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Environmental Science(all)
  • Materials Science(all)
  • Physics and Astronomy(all)


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