SignalSilence ® NF-kappaB p65 siRNA I

Transcription factors of the nuclear factor κB (NF-κB)/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-κB1 (p105/p50), and NF-κB2 (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-κB is sequestered in the cytoplasm by IκB inhibitory proteins (3-5). NF-κB-activating agents can induce the phosphorylation of IκB proteins, targeting them for rapid degradation through the ubiquitin-proteasome pathway and releasing NF-κB to enter the nucleus where it regulates gene expression (6-8). NIK and IKKα (IKK1) regulate the phosphorylation and processing of NF-κB2 (p100) to produce p52, which translocates to the nucleus (9-11).Small Interfering RNA (siRNA) has been used to specifically silence NF-kappaB p65 in colon cancer cells (10). 1.Baeuerle, P.A. and Henkel, T. (1994) Annu Rev Immunol 12, 141-79. 2.Baeuerle, P.A. and Baltimore, D. (1996) Cell 87, 13-20. 3.Haskill, S. et al. (1991) Cell 65, 1281-9. 4.Thompson, J.E. et al. (1995) Cell 80, 573-82. 5.Whiteside, S.T. et al. (1997) EMBO J 16, 1413-26. 6.Traenckner, E.B. et al. (1995) EMBO J 14, 2876-83. 7.Scherer, D.C. et al. (1995) Proc Natl Acad Sci USA 92, 11259-63. 8.Chen, Z.J. et al. (1996) Cell 84, 853-62. 9.Senftleben, U. et al. (2001) Science 293, 1495-9. 10.Coope, H.J. et al. (2002) EMBO J 21, 5375-85. 11.Xiao, G. et al. (2001) Mol Cell 7, 401-9. 12.Verma, U. N. et al. (2003) Clin. Cancer Res. 9, 1291-1300.