Nitric oxide (NO) disrupts specific DNA binding of the transcription factor c-Myb in vitro.

In an attempt to elucidate signal transduction pathways which may modulate DNA binding of the transcription factor c-Myb, we investigated whether c-Myb could be a target for the signaling molecule nitric oxide (NO) in vitro. NO-generating agents severely inhibited specific DNA binding of the c-Myb minimal DNA-binding domain R2R3. This inhibition was readily reversible upon treatment with excess DTT. A redox-sensitive cysteine (C130) was required for this NO sensitivity. Moreover, a DNA-binding domain carrying two of the avian myeloblastosis virus (AMV)-specific mutations (L106H, V117D) appeared to be less sensitive to S-nitrosylation than the wild-type c-Myb. This difference in NO sensitivity may influence the regulation of wild type versus AMV v-Myb protein function.