A NOVEL TRANSCRIPTION FACTOR REGULATES EXPRESSION OF THE VACUOLAR H-ATPASE B2 SUBUNIT THROUGH AP-2 SITES DURING MONOCYTIC DIFFERENTIATION()

During monocyte-to-macrophage differentiation, the cellular content of vacuolar H+-ATPase (V-ATPase) in creases more than 4-fold, We have sh own previously that amplified expression of the B2 subunit of the V-AT Pase occurs solely by increased transcription, and that the 5'-untrans lated region of the B2 gene, containing multiple consensus binding sit es for the transcription factors AP-2 and Sp1, is required for this ex pression. The present study demonstrates that AP-2 binding sequences a re essential for increased transcription from the B2 promoter during m onocyte-macrophage differentiation and that AP-2, expressed exogenousl y in THP-1 and other cells, activates transcription from the B2 promot er. In mobility shift assays, a nuclear factor from THP-1 and U-937 ce lls was identified that binds to several AP-2 response elements within the B2 promoter, but does not react with AP-2 antibodies, and has a D NA sequence binding affinity profile that differs from AP-2. These fin dings suggest that a novel AP-2-like transcription factor is responsib le for V-ATPase B subunit amplification during monocyte differentiatio n.