NITRIC-OXIDE (NO) DISRUPTS SPECIFIC DNA-BINDING OF THE TRANSCRIPTION FACTOR C-MYB IN-VITRO

In an attempt to elucidate signal transduction pathways which mag modu late DNA binding of the transcription factor c-Myb, we investigated wh ether c-Myb could be a target for the signaling molecule nitric oxide (NO) in vitro, NO-generating agents severely inhibited specific DNA bi nding of the c-Myb minimal DNA-binding domain R2R3., This inhibition w as readily reversible upon treatment with excess DTT. A redox-sensitiv e cysteine (C130) was required for this NO sensitivity. Moreover, a DN A-binding domain carrying two of the avian myeloblastosis virus (AMV)- specific mutations (L106H, V117D) appeared to be less sensitive to S-n itrosylation than the wild-type c-Myb. This difference in NO sensitivi ty may influence the regulation of wild type versus AMV v-Myb protein function. (C) 1998 Federation of European Biochemical Societies.