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

Autor: Yvette Roy, Danielle Cadieux, Greg L. Beilhartz, Kelly A. Meckling, Wenqing Wu, Cynthia L. Richard, Mary C. Farach-Carson, Marc G. Coppolino, Ilka Nemere, Lauren Brown, Maureen Curtin
Rok vydání: 2010
Předmět:
Zdroj: Experimental Cell Research. 316:1101-1108
ISSN: 0014-4827
Popis: 1,25 Dihydroxyvitamin D{sub 3} (1,25D{sub 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{sub 3}, which is a distinct gene product from the classical nuclear vitamin D receptor. This 57 kDa protein, named 1,25D{sub 3}-MARRS (Membrane Activated Rapid Response to Steroids)/ERp57/PIA3 appears to associate in a complex with the transcription factor, nuclear factor kappa B (NF{kappa}B). In unstimulated cells, 1,25D{sub 3}-MARRS can be co-immunoprecipitated with antibodies directed at NF{kappa}B, and NF{kappa}B is co-precipitated when antibodies against 1,25D{sub 3}-MARRS or ERp57 are used. Confocal microscopy and subcellular fractionation studies demonstrate that both 1,25D{sub 3}-MARRS and NF{kappa}B begin translocating to the nucleus within minutes of co-stimulation with 1,25D{sub 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{sub 3}-MARRS in the nucleus as a regulator of gene expression. Here it may also regulate the activity of NF{kappa}B and other factors with which it may be interacting.
Databáze: OpenAIRE