PUBLICATION
Zebrafish IkappaB Kinase 1 Negatively Regulates NF-kappaB Activity
- Authors
- Correa, R.G., Matsui, T., Tergaonkar, V., Rodriguez-Esteban, C., Izpisúa Belmonte, J.C., and Verma, I.M.
- ID
- ZDB-PUB-050803-7
- Date
- 2005
- Source
- Current biology : CB 15(14): 1291-1295 (Journal)
- Registered Authors
- Izpisúa Belmonte, Juan Carlos, Matsui, Takaaki, Rodriguez-Esteban, Concepcion
- Keywords
- none
- MeSH Terms
-
- Animals
- Blotting, Western
- Cell Line
- Chromosome Mapping
- Cloning, Molecular
- Computational Biology
- DNA Primers
- Down-Regulation*
- Gene Components
- Humans
- I-kappa B Kinase
- Immunohistochemistry
- In Situ Hybridization
- NF-kappa B/metabolism*
- Protein Serine-Threonine Kinases/genetics
- Protein Serine-Threonine Kinases/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction/physiology*
- Zebrafish/metabolism*
- PubMed
- 16051172 Full text @ Curr. Biol.
Citation
Correa, R.G., Matsui, T., Tergaonkar, V., Rodriguez-Esteban, C., Izpisúa Belmonte, J.C., and Verma, I.M. (2005) Zebrafish IkappaB Kinase 1 Negatively Regulates NF-kappaB Activity. Current biology : CB. 15(14):1291-1295.
Abstract
The IkappaB kinase (IKK) activity is critical for processing IkappaB inhibitory proteins and activating the NF-kappaB signaling, which is involved in a series of physiological and developmental steps in vertebrates. The IKK activity resides in two catalytic subunits, IKK1 and IKK2, and two regulatory subunits, NEMO and ELKS. IKK2 is the major cytokine-responsive IkappaB kinase because depletion of IKK1 does not interfere with the IKK activity. In fact, IKK1(-/-) mice display morphological abnormalities that are independent of its kinase activity and NF-kappaB activation. Hence, using zebrafish (Danio rerio) as a model, we examined the evolutionary role of IKK1 in modulating NF-kappaB. Ikk1(-/-) zebrafish embryos present head and tail malformations and, surprisingly, show upregulation of NF-kappaB-responsive genes and increased NF-kappaB-dependent apoptosis. Overexpression of ikk1 leads to midline structure defects that resemble NF-kappaB blockage in vivo. Zebrafish Ikk1 forms complexes with NEMO that represses NF-kappaB in vertebrate cells. Indeed, truncation of its NEMO binding domain (NBD) restores NF-kappaB-dependent transcriptional activity and, consequently, the ikk1-overexpressing phenotype. Here, we report that Ikk1 negatively regulates NF-kappaB by sequestering NEMO from active IKK complexes, indicating that IKK1 can function as a repressor of NF-kappaB.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping