NF-κB transcription factors are pivotal players in controlling inflammatory and 
immune responses, as well as cell proliferation and apoptosis. Aberrant 
regulation of NF-κB and the signaling pathways that regulate its activity have 
been involved in various pathologies, particularly cancers, as well as 
inflammatory and autoimmune diseases. NF-κB activation is tightly regulated by 
the IκB kinase (IKK) complex, which is composed of two catalytic subunits IKKα 
and IKKβ, and a regulatory subunit IKKγ/NEMO. Although IKKα and IKKβ share 
structural similarities, IKKα has been shown to have distinct biological 
functions. However, the molecular mechanisms that modulate IKKα activity have 
not yet been fully elucidated. To understand better the regulation of IKKα 
activity, we purified IKKα-associated proteins and identified ABIN-2. Here, we 
demonstrate that IKKα and IKKβ both interact with ABIN-2 and impair its 
constitutive degradation by the proteasome. Nonetheless, ABIN-2 enhances IKKα- 
but not IKKβ-mediated NF-κB activation by specifically inducing IKKα 
autophosphorylation and kinase activity. Furthermore, we found that ABIN-2 
serine 146 is critical for the ABIN-2-dependent IKKα transcriptional 
up-regulation of specific NF-κB target genes. These results imply that ABIN-2 
acts as a positive regulator of NF-κB-dependent transcription by activating 
IKKα.