1,25 Dihydroxyvitamin D(3) (1,25D(3)) primes NB4 promyelocytic leukemia cells to differentiate along the monocyte/macrophage lineage through a non-genomic mechanism. Here we show that NB4 cells express high levels of the recently identified membrane receptor for 1,25D(3), which is a distinct gene product from the classical nuclear vitamin D receptor. This 57 kDa protein, named 1,25D(3)-MARRS (Membrane Activated Rapid Response to Steroids)/ERp57/PIA3 appears to associate in a complex with the transcription factor, nuclear factor kappa B (NFkappaB). In unstimulated cells, 1,25D(3)-MARRS can be co-immunoprecipitated with antibodies directed at NFkappaB, and NFkappaB is co-precipitated when antibodies against 1,25D(3)-MARRS or ERp57 are used. Confocal microscopy and subcellular fractionation studies demonstrate that both 1,25D(3)-MARRS and NFkappaB begin translocating to the nucleus within minutes of co-stimulation with 1,25D(3) and phorbol ester. The predominant nuclear localization of both proteins precedes the expression of the monocyte/macrophage phenotype and suggests that this event may be critical to the differentiation pathway. This suggests a role for 1,25D(3)-MARRS in the nucleus as a regulator of gene expression. Here it may also regulate the activity of NFkappaB and other factors with which it may be interacting.
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