Nucleic Acids, Protein Synthesis, and Molecular Genetics
A Novel Transcription Factor Regulates Expression of the Vacuolar H+-ATPase B2 Subunit through AP-2 Sites during Monocytic Differentiation*

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During monocyte-to-macrophage differentiation, the cellular content of vacuolar H+-ATPase (V-ATPase) increases more than 4-fold. We have shown previously that amplified expression of the B2 subunit of the V-ATPase occurs solely by increased transcription, and that the 5′-untranslated region of the B2 gene, containing multiple consensus binding sites for the transcription factors AP-2 and Sp1, is required for this expression. The present study demonstrates that AP-2 binding sequences are essential for increased transcription from the B2 promoter during monocyte-macrophage differentiation and that AP-2, expressed exogenously in THP-1 and other cells, activates transcription from the B2 promoter. In mobility shift assays, a nuclear factor from THP-1 and U-937 cells 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 DNA sequence binding affinity profile that differs from AP-2. These findings suggest that a novel AP-2-like transcription factor is responsible for V-ATPase B subunit amplification during monocyte differentiation.

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*

This work was supported in part by National Institutes of Health Grants AR32087, DK38848, DK09976, and DK45181 and by a research grant from the Arthritis Foundation (to B. S. L). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

2

R. D. Nelson, D. M. Underhill, S. P. Hmiel, S. Bae, and S. L. Gluck, submitted for publication.

3

B. S. Lee and S. L. Gluck, unpublished results.