International Journal of Molecular Medical Science, 2024, Vol.14, No.1, 24-28 http://medscipublisher.com/index.php/ijmms 24 Scientific Review Open Access Glucocorticoid Receptor Signaling: Intricacies and Therapeutic Opportunities ShudanYan Biotechnology Research Center, Cuixi Academy of Biotechnology, Zhuji, 311800, China Corresponding email: alinasdyan2024@gmail.com International Journal of Molecular Medical Science, 2024, Vol.14, No.1 doi: 10.5376/ijmms.2024.14.0004 Received: 01 Mar., 2024 Accepted: 08 Mar., 2024 Published: 12 Mar., 2024 Copyright © 2024 Yan, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Yan S.D., 2024, Glucocorticoid receptor signaling: intricacies and therapeutic opportunities, International Journal of Molecular Medical Science, 14(1): 24-28 (doi: 10.5376/ijmms.2024.14.0004) The paper "Glucocorticoid receiver signing: intricacies and thermal opportunities" published in the journal Trends in Biochemical Sciences on February 29, 2024, authored by Dorien Clarisse, Laura Van Moortel, Chlo é Van Leene, Kris Gevaert, Karolin De Bosscher, and others from the University of Bridget et al. This study delves into the signaling mechanism of glucocorticoid receptors (GR) and their potential therapeutic applications. GR, as a nuclear receptor (NR), plays a crucial role in regulating the treatment of inflammatory diseases and certain cancers. By reviewing the basic biological characteristics of GR, including its activation and nuclear translocation mechanisms in cells, this study discusses in detail the interaction between GR and chromatin, revealing how it regulates downstream gene expression by directly binding to DNA responsive elements or interacting with other transcription factors. In addition, new concepts in GR signaling were explored, such as the recruitment of co regulatory factors, the role of aggregate formation, and strategies to enhance therapeutic efficacy through interaction with other nuclear receptors. By integrating multiple technologies to study the conformation and modification of chromatin, we can gain a deeper understanding of the cell-specific effects of glucocorticoids (GCs), providing a new perspective for developing GR ligands and therapeutic strategies with fewer side effects. This study not only provides valuable insights into the complex role of GR in cells, but also provides a theoretical basis for the development of new therapeutic methods in the future, especially in research aimed at reducing treatment-related side effects while improving efficacy. 1 Experimental Data Analysis This study provides a detailed description of the structure of GR, including its inter domain communication when binding to different ligands, and how it affects the interaction between GR and chromatin. By integrating technology to study chromosome conformation, accessibility, modification, and recruitment of cofactors, we can gain a deeper understanding of the cell-specific effects of glucocorticoids (GCs). Research has found that dimerization and allosteric communication in the GR field are crucial for the efficacy of glucocorticoids, and chromosome remodeling complexes are crucial for fine-tuning GR activity. Figure 1 shows the diverse mechanisms of action of glucocorticoid receptors (GR). GR is mainly located in the cytoplasm when ligands are not bound, and exists in a partially unfolded state, preventing ligand binding through the Hsp70-Hsp40 chaperone complex. Subsequently, GR will undergo a series of complex transformations, ultimately forming an Hsp90-GR-FKBP52 nuclear transfer complex that can transfer to the nucleus. As a transcription factor, GR can mediate gene activation or inhibition. The inhibitory effect is usually achieved through interaction with other transcription factors, such as NF-κB The interaction between B and AP-1 is achieved, thereby inhibiting their activity. The mechanisms by which GR activates and inhibits gene expression are diverse, including direct DNA binding and indirect mediation or isolation of transcription factors through other transcription factors.
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