Antigen:
His-tagged full-length human IKKγ
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Clone designation:
72C627
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Host:
mouse
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Isotype:
IgG1
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Application(s):
WB
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Nuclear Factor-κB (NF-κB) is sequestered in the cytoplasm by the IκB family of inhibitory proteins that mask the nuclear localization signal of NF-κB, thereby preventing translocation of NF-κB to the nucleus.1 External stimuli such as tumor necrosis factor or other cytokines result in phosphorylation and degradation of IκB, releasing NF-κB dimers. NF-κB dimers subsequently translocate to the nucleus and activate target genes. Synthesis of IκBα is autoregulated.2 IκB proteins are phosphorylated by IκB kinase complex consisting of at least three proteins, IKK1/α, IKK2/β, and IKK3/γ.3,4,5,6,7 IKKγ preferentially interacts with IKKβ and is required for activation of IKK complex. IKKγ is also known as NF-κB essential modulator (NEMO).7 The human T-cell leukemia virus type I Tax oncoprotein that activates NF-κB binds neither to IKKα nor IKKβ, but complexes directly with IKKγ.8 This suggests that IKKγ may be a key molecule acting as an adapter for oncoprotein specific signaling to IKKα and IKKβ.8
1
Verma, I.M., Stevenson, J.K., Schwarz, E.M., et al. Rel/NF-κB/IκB family: Intimate tales of association and dissociation. Genes Dev 9 2723-2735 (1995).
2
Verma, I.M., and Stevenson, J. IκB kinase: Beginning, not the end. Proc Natl Acad Sci USA 94 11758-11760 (1997).
3
DiDonato, J.A., Hayakawa, M., Rothwarf, D.M., et al. A cytokine-responsive IκB kinase that activates the transcription factor NF-κB. Nature 388 548-554 (1997).
4
Régnier, C.H., Song, H.Y., Gao, X., et al. Identification and characterization of an IκB kinase. Cell 90 373-383 (1997).
5
Mercurio, F., Zhu, H., Murray, B.W., et al. IKK-1 and IKK-2: Cytokine-activated IκB kinases essential for NF-κB activation. Science 278(5339) 860-866 (1997).
6
Rothwarf, D.M., Zandi, E., Natoli, G., et al. IKK-γ is an essential regulatory subunit of the IκB kinase complex. Nature 395 297-300 (1998 1998).
7
Yamaoka, S., Courtois, G., Bessia, C., et al. Complementation cloning of NEMO, a component of the IκB kinase complex essential for NF-κB activation. Cell 93 1231-1240 (1998).
8
Jin, D.Y., Giordano, V., Kibler, K.V., et al. Role of adapter function in oncoprotein-mediated activation of NF-kB. J Biol Chem 274(25) 17402-17405 (1999 Mar 16 1999).
