Nuclear translocation of the 1,25D3-MARRS (membrane associated rapid response to steroids) receptor protein and NFκB in differentiating NB4 leukemia cells

1,25 Dihydroxyvitamin D3 (1,25D3) 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 1,25D3, which is a distinct gene product from the classical nuclear vitamin D receptor. This 57 kDa protein, named 1,25D3-MARRS (Membrane Activated Rapid Response to Steroids)/ERp57/PIA3 appears to associate in a complex with the transcription factor, nuclear factor kappa B (NFκB). In unstimulated cells, 1,25D3-MARRS can be co-immunoprecipitated with antibodies directed at NFκB, and NFκB is co-precipitated when antibodies against 1,25D3-MARRS or ERp57 are used. Confocal microscopy and subcellular fractionation studies demonstrate that both 1,25D3-MARRS and NFκB begin translocating to the nucleus within minutes of co-stimulation with 1,25D3 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 1,25D3-MARRS in the nucleus as a regulator of gene expression. Here it may also regulate the activity of NFκB and other factors with which it may be interacting.