SNIP1 inhibits NF-kappa B signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional Co-activators

SNIP1 is a 396-amino acid nuclear protein shown to be an inhibitor of the T GF-beta signal transduction. pathway and to be important in suppressing tra nscriptional activation dependent on the co-activators CBP and p300. In thi s report we show that SNIP1 potently inhibits the activity of NF-kappaB, wh ich binds the C/H1 domain of CBP/p300, but does not interfere with the acti vity of transcription factors such as p53, which bind to other domains of p 300, or factors such as VP16, which are independent of these co-activators. Inhibition of NF-kappaB activity is a function of the N-terminal domain of SNIP1 and involves competition of SNIP1 and the NF-kappaB subunit, RelA/p6 5, for binding to p300, similar to the mechanism of inhibition of Smad sign aling by SNIP1. Immunohistochemical staining shows that expression of SNIP1 is strictly regulated in development and that it colocalizes, in certain t issues, with nuclear staining for RelA/p65 and for p300, suggesting that th ey may regulate NF-kappaB activity in vivo in a spatially and temporally co ntrolled manner. These data led us to suggest that SNIP1 may be an inhibito r of multiple transcriptional pathways that require the C/H1 domain of CBP/ p300.