Description
Background: Transcription factors of the nuclear factor kappa B (NF-kappaB)/Rel family play a pivotal role in inflammatory and immune responses (1,2). There are five family members in mammals: RelA, c-Rel, RelB, NF-kappaB1 (p105/p50), and NF-kappaB2 (p100/p52). Both p105 and p100 are proteolytically processed by the proteasome to produce p50 and p52, respectively. Rel proteins bind p50 and p52 to form dimeric complexes that bind DNA and regulate transcription. In unstimulated cells, NF-kappaB is sequestered in the cytoplasm by IkappaB inhibitory proteins (3-5). NF-kappaB-activating agents can induce the phosphorylation of IkappaB proteins, targeting them for rapid degradation through the ubiquitin-proteasome pathway and releasing NF-kappaB to enter the nucleus where it regulates gene expression (6-8). NIK and IKKalpha (IKK1) regulate the phosphorylation and processing of NF-kappaB2 (p100) to produce p52, which is then translocated to the nucleus (9-11). NF-kappaB assembly with IkappaB, as well as its DNA binding and transcriptional activity, are regulated by p300/CBP acetytransferases that principally target Lys218, Lys221 and Lys310 (12-14). This process is reciprocally regulated by histone deacetylases (HDACs); several HDAC inhibitors have been shown to activate NF-kappaB (12-14)