Model of Tax-induced SHP-1 P2 promoter silencing (TIPS). In the absence of Tax (A), PKA (protein kinase A) phosphorylates IκB and leads to IκB degradation. NF-κB is released and subsequently phosphorylated and dimerized. The dimerized NF-κB translocates into the nucleus, binds to the NF-κB motifs on the promoter, and is further acetylated by CBP/p300. RNA polymerase II (RNAP II) is recruited to the promoter to form a transcriptional complex (TC). The SHP-1 P2 promoter is thus activated and generates luciferase activity. The presence of Tax (B) serves to recruit HDAC1, and probably other inhibitory molecules onto the SHP-1 P2 promoter to form an inhibitory complex (IC) at the sequence within or surrounding the 2 NF-κB motifs. Tax-associated HDAC1 also deacetylates NF-κB, and reduces the binding of NF-κB on Tax and its association with P2 promoter. The promoter is converted into a “locked” pattern and is therefore silenced. Moreover, inhibition of PKA-induced IκB phosphorylation and degradation may also occur in the presence of Tax, which prevents NF-κB from being activated. On the other hand, mutation of either NF-κB motif (only one is illustrated) will prevent Tax-IC complex formation (C), and the promoter is opened in an “unlocked” position thereby leading to a loss of TIPS effect.