Authors: Khanal, R. C.; Nemere, I.

Source: Current Medicinal Chemistry, Volume 14, Number 10, April 2007 , pp. 1087-1093(7)

Publisher: Bentham Science Publishers

Abstract:

ERp57/GRp58 is a thiol-protein disulphide oxidoreductase and has been studied in many clinically relevant systems, both as a chaperone protein and as a membrane receptor for the steroid hormone, 1,25(OH)2D3. Our laboratory investigates phenomena associated with rapid, membrane-initiated signaling by steroid hormones synthesized from vitamin D (cholecalciferol). We have recently reported that the cell surface receptor for the metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], which we have termed the 1,25D3-MARRS (Membrane Associated, Rapid Response Steroid binding) receptor, is in fact identical to ERp57/GRp58. Here we review the dynamic role ERp57/GRp58/1,25D3-MARRS receptor plays in a variety of cellular processes. Starting with its structure at the DNA and protein levels, we review the available literature about its role as a chaperone protein, in immune function through the assembly of MHC class I molecules, DNA binding, and its function as the 1,25D3-MARRS receptor. Finally, we present the role it may play in relation to important disease states. While ERp57/GR58/1,25D3-MARRS receptor is a pivotal protein in many cell functions, it has yet to be determined whether-and to what extent-these phenomena are regulated by the vitamin D endocrine system. However, 1,25(OH)2D3 is involved in differentiation of certain cancer cells and in muscle function, and ERp57/1,25D3-MARRS protein has been reported to be involved in such processes. Thus, medicinal chemistry aimed at the 1,25D3-MARRS receptor in lymphocytes, cancer cells, bone, intestinal epithelia, and kidney may add to the current therapeutic regimens for various disease states.

Keywords: Thiol:protein disulphide oxidoreductase; PDIA3; ERp57; GRp58; 1,25D3-MARRS receptor; Vitamin D; chaperone; immune system; diseases; DNA binding

Document Type: Research article

DOI: http://dx.doi.org/10.2174/092986707780362871

Affiliations: 1: Department of Nutrition and Food Sciences,Utah State University, Logan, UT 84322-8700, USA.

Publication date: 2007-04-01

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• Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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