Inhibitor of the inflammatory response induced by TNFamp;agr; and IL-1

摘要

The present invention provides the molecular basis for cytokine induction of NF-&kgr;B-dependent immune and inflammatory responses, emphasizing a role for both NIK-NIK and NIK-IKK protein—protein interactions. A relatively small region of NIK selectively impairs the NIK-IKK interaction. The present invention provides a novel and highly specific method for modulating NF-&kgr;B-dependent immune, inflammatory, and anti-apoptotic responses, based on interruption of the critical protein—protein interaction of NIK and IKK. The present invention provides methods for inhibiting NF-&kgr;B-dependent gene expression, using mutant NIK proteins. One embodiment of the present invention provides kinase-deficient NIK mutant proteins that inhibit activation of IKK. Another embodiment of the invention provides N-terminus NIK mutant proteins that bind IKK, thus inhibiting NIK/IKK interaction.