Inhibition of NF-kappaB activation with designed ankyrin-repeat proteins targeting the ubiquitin-binding/oligomerization domain of NEMO.

ABSTRACT: The link between the NF-kappaB signal transduction pathway and cancer is now well established. Inhibiting this pathway is therefore a promising approach in the treatment of certain cancers through a pro-apoptotic effect in malignant cells. Owing to its central role in the pathway, the IkappaB kinase (IKK) complex is a privileged target for designing inhibitors. Previously, we showed that oligomerization of NEMO is necessary for IKK activation and defined a minimal oligomerization domain (CC2-LZ) for NEMO, and we developed NEMO peptides inhibiting NF-kappaB activation at the level of the IKK complex. To improve the low-affinity inhibitors, we used ribosome display to select small and stable proteins with high affinity against the individual CC2-LZ because the entire NEMO protein is poorly s

SUBMITTER: Wyler E 

PROVIDER: S-EPMC2206981 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature