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Constitutive DNA Binding of the Low Mobility Forms of the AP-1 and SP-1 Transcription Factors in HL60 Cells Resistant to 1-ß-D-Arabinofuranosylcytosine¹

Department of Laboratory Medicine and Pathology, UMD-New Jersey Medical School, Newark, New Jersey 07103

DNA binding of the AP-1 transcription factor, a dimer of jun-fos or jun-jun proteins, is regulated during monocytic differentiation of HL60 cells. The abundance of AP-1 complexes capable of binding to DNA increases and complexes with slow electrophoretic mobility appear after exposure of HL60 cells to 1,25-dihydroxyvitamin D₃. Similar changes are seen in the SP-1 transcription factor. In contrast, variants of HL60 cells that are resistant to both 1,25-dihydroxyvitamin D₃ and 1-ß-D-arabinofuranosylcytosine constitutively express the slowly migrating AP-1 and SP-1 complexes which are found only in the differentiated parental HL60 cells. Because this form of AP-1 complex is highly phosphorylated, the data show that altered phosphorylation of at least two transcription factors is associated with resistance to 1-ß-D-arabinofuranosylcytosine.

¹ This work was supported by National Cancer Institute Grant RO1 CA-44722, New Jersey Commission on Cancer Research Grant 92-44, and a grant from the Ruth Estrin Goldberg Foundation.

² To whom requests for reprints should be addressed, at Department of Laboratory Medicine and Pathology, UMD-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103.

Received 12/14/93. Accepted 2/ 4/93.

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