Constitutive DNA binding of the low mobility forms of the AP-1 and SP-1 transcription factors in HL60 cells resistant to 1-beta-D-arabinofuranosylcytosine.
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-beta-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-beta-D-arabinofuranosylcytosine.
Kolla
S S
SS
Department of Laboratory Medicine and Pathology, UMD-New Jersey Medical School, Newark 07103.
Studzinski
G P
GP
D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D004351:Drug Resistance / Q000502:physiology; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D016755:Proto-Oncogene Proteins c-jun; D016329:Sp1 Transcription Factor; D003561:Cytarabine