The activating protein-1 (AP-1)
transcription factor complex is a heterogeneous entity, composed in mammalian cells of dimers chosen from a group of at least eight
proteins belonging to three families: jun, fos, and activating
transcription factor (ATF). The
AP-1 complexes participate in diverse biological processes that include cell proliferation, survival, and differentiation. These seemingly contrasting functions have been attributed to the intensity and duration of the signals provided by
AP-1, but the biological consequences of changing composition of the
AP-1 complex have not been fully explored. Here, we show that functional
AP-1 is required for
1,25-dihydroxyvitamin D3 (1,25D)-induced monocytic differentiation, and that the composition of the
AP-1 protein complex that binds TRE, its cognate
DNA element, changes as cells differentiate. In HL60 cells in an early stage of differentiation, the principal
AP-1 components detected by gel shift analysis include c-jun, ATF-2, fos-B, fra-1, and fra-2. In cells with a more established monocytic phenotype, the demonstrable
AP-1 components are c-jun, ATF-2, jun-B, and fos-B. Following the addition of 1 nmol/L of 1,25D, the cellular content of each of these four
proteins markedly increased in a sustained manner, whereas the increases in c-fos, fra-1, fra-2, and jun-D were minimal, if any. Small increases in
mRNA levels encoding all
AP-1 component
proteins, except c-fos, were also noted. These findings provide a basis for the previously found participation of the
c-Jun N-terminal kinase pathway in 1,25D-induced differentiation of
myeloid leukemia cells, and direct attention to jun-B and fos-B as new cellular therapeutic targets, that may promote replicative quiescence associated with differentiation of malignant cells.