IKB
The NF-kappa-B (NFKB) complex of proteins is inhibited by I-kappa-B (IKB) proteins, which inactivate NFKB by trapping it in the cytoplasm. Phosphorylation of serine residues on the IKB proteins by IKB kinases marks them for destruction via the ubiquitination pathway, thereby allowing activation and nuclear translocation of the NFKB complex. The protein encoded by this gene is similar to IKB kinases and can mediate NFKB activation in response to certain growth factors. For example, the protein can form a complex with the IKB protein TANK and TRAF2 and release the NFKB inhibition caused by TANK.
The
transcription factor NF-kappaB is implicated in
various aspects of T cell development and function. The IkappaB
kinase (IKK) complex, consisting of two kinases, IKK1/alpha and IKK2/beta, and the NEMO/IKKgamma regulatory subunit, mediates NF-kappaB activation by most known stimuli. Adoptive transfer
experiments had demonstrated that IKK1 and IKK2 are dispensable for T cell
development. We show here that T lineage-specific deletion of IKK2 allows
survival of naive peripheral T cells but interferes with the generation of
regulatory and memory T cells. T cell-specific ablation of NEMO or replacement of IKK2 with a kinase-dead
mutant prevent development of peripheral T cells altogether. Thus,
IKK-induced NF-kappaB activation, mediated by either
IKK1 or IKK2, is essential for the generation and survival of mature T cells,
and IKK2 has an additional role in regulatory and memory T cell
development.