IKAP (Central region)

The NF-k B transcription factor coordinates a response to pathogens and pro-inflammatory cytokines, and is vital in the development of acute and chronic inflammatory diseases. NF-k B is activated by cytokine-activated IKB kinases (IKKs) found in large complexes. The IKK complexes consist of NIK, IKK-a, IKK-b , IkB-a, NF-k B/RelA and IKK-complex-associated protein (IKAP). First identified as a scaffolding protein of the IKK complex, IKAP, also known as elongation protein 1 (ELP1), has been linked to adhesion and migration in several cell types, including rat primary neurons. Depletion of IKAP by loss-of-function mutations in the IKBKAP gene has been shown to cause defective neuronal development and maintenance, leading to familial dysautonomia (FD). FD is a hereditary neuronal disease characterized by poor development and progressive degeneration of the sensory and autonomic nervous system. In addition, IKAP associates with c-Jun N-terminal kinase (JNK) and could specifically enhance JNK activation induced by the upstream JNK activators MEKK1 and ASK1, indicating another possible cause for FD.

References