Tax 7ransActivation of Nuclear Factor kB

Nuclear factor kB (NF-kB) is an important rapid response transcription factor that is common to all cell types45 (Figure 12-7). NF-kB related proteins dimerize in the cytoplasm but are inhibited from translocating into the nucleus by the inhibi tion of kB (IkB) protein, which binds to the dimer and masks its nuclear localization sequence (NLS). Certain stimuli can activate inhibitor of kB kinases (IKKs). These kinases phos-phorylate IkB causing it to dissociate from NF-kB. At this point, NF-kB can migrate to the nucleus and trans-activate a number of cellular genes. The phosphorylated form of IkB is susceptible to polyubiquination, which targets it to the proteo-some for degradation.

HTLV Tax is known to stimulate the activation of NF-kB at several levels in this pathway (Figure 12-7). Tax acts to free NF-kB from cytoplasmic constraints by causing its dissociation via the activation of IKKs and, presumably, by acting as a molecular chaperone due to its ability to bind both the phosphorylated form of IkB and the proteosome.46'47 By this mechanism, Tax would be able to guide IkB to the proteo-some to promote its degradation and prevent further association with other cytoplasmic NF-kB dimers. Tax also enhances the trans-activating capabilities of NF-kB by stimulating dimerization and strengthening the binding of NF-kB to promoter elements.48

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