NF-kB is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins, called IkBs, which mask the nuclear localization signal (NLS) of NF-kB and prevent its nuclear translocation. A key event in NF-kB activation involves phosphorylation of IkB (at sites equivalent to Ser32 and Ser36 of IkB-alpha or Ser19 and Ser22 of IkB-beta) by IKK. The phosphorylated IkB-alpha is recognized by the E3 ligase complex and targeted for ubiquitin-mediated proteasomal degradation, releasing the NF-kB dimer p50/p65 into the nucleus to turn on target genes. (Karin & Ben-Neriah 2000)
Rothwarf, DM, Karin, M, Zandi, E, DiDonato, JA, Hayakawa, M
Sakurai, H, Pappu, BP, Hara, H, Li, H, Lin, X, Darnay, BG, Shambharkar, PB, You, Y, Blonska, M, Penninger, J
Karin, M, Bonizzi, G
Hayden, MS, Ghosh, S
Parent, L, Chen, ZJ, Maniatis, T
protein serine/threonine kinase activity of p-S177,S181-IKKB:IKKA:pUb-NEMO [cytosol]
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