A New Regulatory Mechanism of NF-κB Activation by I-κBβ in Cancer Cells

Jung Mo Kim, Reinhard E. Voll, Chunkyu Ko, Dae Seok Kim, Kang Seo Park, Soo Youl Kim

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Transglutaminase 2 (TGase 2) catalyzes covalent isopeptide bond formation between glutamine and lysine residues. Recently, we reported that TGase 2 activates nuclear factor-kappa B (NF-κB) by depleting inhibitor of NF-κBα (I-κBα) levels via polymer formation. Furthermore, TGase 2 expression synergistically increases NF-κB activity with canonical pathway. The major I-κB proteins such as I-κBα and I-κBβ resemble each other in both primary sequence and tertiary structure. However, I-κBβ does not degrade fully, while I-κBα degrades immediately in response to most stimuli. We found that I-κBβ does not contain any of the previously identified TGase 2 target sites. In this study, both an in vitro cross-linking assay and a TGase 2 transfection assay revealed that I-κBβ is independent from TGase 2-mediated polymerization. Furthermore, increased I-κBβ expression reversed NF-κB activation in cancer cells, compensating for the loss of I-κBα via TGase 2 polymerization.

Original languageEnglish (US)
Pages (from-to)756-765
Number of pages10
JournalJournal of Molecular Biology
Volume384
Issue number4
DOIs
StatePublished - Dec 26 2008
Externally publishedYes

Keywords

  • I-κBα
  • I-κBβ
  • NF-κB
  • polymerization
  • transglutaminase 2

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'A New Regulatory Mechanism of NF-κB Activation by I-κBβ in Cancer Cells'. Together they form a unique fingerprint.

  • Cite this