Nuclear factor (NF)-κB is a ubiquitous and essential transcription factor whose dysregulation has been linked to numerous diseases including arthritis and cancer. It is therefore not surprising that the NF-κB activation pathway has become a major target for development of novel therapies for inflammatory diseases and cancer. However, the indispensable role played by NF-κB in many biological processes has raised concern that a complete shutdown of this pathway would have significant detrimental effects on normal cellular function. Instead, drugs that selectively target the inflammation induced NF-κB activity, while sparing the protective functions of basal NF-κB activity, would be of greater therapeutic value and would likely display fewer undesired side effects. The recent identification and characterisation of the NF-κB essential modulator (NEMO)-binding domain (NBD) peptide that can block the activation of the IκB kinase (IKK) complex, have provided an opportunity to selectively abrogate the inflammation induced activation of NF-κB by targeting the NBD–NEMO interaction. This peptide is synthesised in tandem with a protein transduction domain sequence from Drosophila antennapedia which facilitates uptake of the inhibitory peptide into the cytosol of target cells.
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- CIA, collagen induced arthritis
- IL, interleukin
- NBD, NEMO binding domain
- NEMO, NF-κB essential modulator
- NF-κB nuclear factor (NF)-κB
- IKK, IκB kinases
- NKK, NF-κB inducing kinase
- LT, lymphotoxin
- nuclear factor (NF)-κB
- TNF, tumour necrosis factor
- WT, wild-type
Competing interests: none declared
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