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Title: Nuclear translocation of the 1,25D{sub 3}-MARRS (membrane associated rapid response to steroids) receptor protein and NF{kappa}B in differentiating NB4 leukemia cells

Abstract

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.

Authors:
; ; ; ; ; ;  [1];  [2];  [3];  [4]
  1. Departments of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada)
  2. Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada N1G2W1 (Canada)
  3. Department of Biological Sciences, University of Delaware, Newark, DE 19716 (United States)
  4. Department of Nutrition and Food Sciences, Center for Integrated BioSystems, Utah State University, Logan, UT 84322 8700 (United States)
Publication Date:
OSTI Identifier:
22212064
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 316; Journal Issue: 7; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIBODIES; FRACTIONATION; GENES; HORMONES; LEUKEMIA; MACROPHAGES; MICROSCOPY; MONOCYTES; PHENOTYPE; PHORBOL ESTERS; RECEPTORS; STEROIDS; TRANSCRIPTION FACTORS; TRANSLOCATION; VITAMIN D

Citation Formats

Wu, Wenqing, Beilhartz, Greg, Roy, Yvette, Richard, Cynthia L., Curtin, Maureen, Brown, Lauren, Cadieux, Danielle, Coppolino, Marc, Farach-Carson, Mary C., Nemere, Ilka, and Meckling, Kelly A., E-mail: kmecklin@uoguelph.ca. Nuclear translocation of the 1,25D{sub 3}-MARRS (membrane associated rapid response to steroids) receptor protein and NF{kappa}B in differentiating NB4 leukemia cells. United States: N. p., 2010. Web. doi:10.1016/J.YEXCR.2010.01.010.
Wu, Wenqing, Beilhartz, Greg, Roy, Yvette, Richard, Cynthia L., Curtin, Maureen, Brown, Lauren, Cadieux, Danielle, Coppolino, Marc, Farach-Carson, Mary C., Nemere, Ilka, & Meckling, Kelly A., E-mail: kmecklin@uoguelph.ca. Nuclear translocation of the 1,25D{sub 3}-MARRS (membrane associated rapid response to steroids) receptor protein and NF{kappa}B in differentiating NB4 leukemia cells. United States. https://doi.org/10.1016/J.YEXCR.2010.01.010
Wu, Wenqing, Beilhartz, Greg, Roy, Yvette, Richard, Cynthia L., Curtin, Maureen, Brown, Lauren, Cadieux, Danielle, Coppolino, Marc, Farach-Carson, Mary C., Nemere, Ilka, and Meckling, Kelly A., E-mail: kmecklin@uoguelph.ca. 2010. "Nuclear translocation of the 1,25D{sub 3}-MARRS (membrane associated rapid response to steroids) receptor protein and NF{kappa}B in differentiating NB4 leukemia cells". United States. https://doi.org/10.1016/J.YEXCR.2010.01.010.
@article{osti_22212064,
title = {Nuclear translocation of the 1,25D{sub 3}-MARRS (membrane associated rapid response to steroids) receptor protein and NF{kappa}B in differentiating NB4 leukemia cells},
author = {Wu, Wenqing and Beilhartz, Greg and Roy, Yvette and Richard, Cynthia L. and Curtin, Maureen and Brown, Lauren and Cadieux, Danielle and Coppolino, Marc and Farach-Carson, Mary C. and Nemere, Ilka and Meckling, Kelly A., E-mail: kmecklin@uoguelph.ca},
abstractNote = {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.},
doi = {10.1016/J.YEXCR.2010.01.010},
url = {https://www.osti.gov/biblio/22212064}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 7,
volume = 316,
place = {United States},
year = {Thu Apr 15 00:00:00 EDT 2010},
month = {Thu Apr 15 00:00:00 EDT 2010}
}