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 language | English (US) |
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Pages (from-to) | 756-765 |
Number of pages | 10 |
Journal | Journal of Molecular Biology |
Volume | 384 |
Issue number | 4 |
DOIs | |
State | Published - Dec 26 2008 |
Externally published | Yes |
Keywords
- I-κBα
- I-κBβ
- NF-κB
- polymerization
- transglutaminase 2
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology