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Mechanisms Of Non-Canonical Nf-Kappab Regulation, Carolyn Margaret Gray

Publicly Accessible Penn Dissertations

NF-kappaB is activated through two signaling cascades: the classical and non-canonical pathways, which are distinguished based on the Inhibitor of kappaB Kinase (IKK) components required to activate each pathway. Whereas classical NF-kappaB requires NF-kappaB Essential Modulator (NEMO) and IKKbeta, non-canonical NF-kappaB requires IKKalpha and upstream stabilization of NF-kappaB Inducing Kinase (NIK), but not NEMO. However, we have previously shown that IKKalpha contains a functional NEMO binding domain and associates with NEMO and IKKbeta as part of the heterotrimeric IKK complex. The overarching goal of the work described in this thesis was to determine whether the interaction between NEMO and IKKalpha …