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

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• 作者：Wenqing Wu ; Greg Beilhartz ; Yvette Roy ; Cynthia L. Richard ; Maureen Curtin ; Lauren Brown ; Danielle Cadieux ; Marc Coppolino ; Mary C. Farach-Carson ; Ilka Nemere ; Kelly A. Meckling
• 关键词：Vitamin D₃ ; Monocyte ; Macrophage ; Acute promyelocytic leukemia ; Confocal microscopy ; Hormone signaling ; Trafficking
• 刊名：Experimental Cell Research
• 出版年：2010
• 出版时间：15 April 2010
• 年：2010
• 卷：316
• 期：7
• 页码：1101-1108
• 全文大小：565 K

文摘

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 (NF;a;B). In unstimulated cells, 1,25D₃-MARRS can be co-immunoprecipitated with antibodies directed at NF;a;B, and NF;a;B 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 NF;a;B 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 NF;a;B and other factors with which it may be interacting.