Rexinoids Induce Differential Gene Expression in Human Glioblastoma Cells and Protein-Protein Interactions in a Yeast Two-Hybrid System.

Autor:	Hackney JF; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Broatch JE; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Dallal RA; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Brotherson C; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Livingston S; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Sabir Z; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Reshi SM; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Faltermeier Petras SR; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Mallick S; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Applegate MT; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Mellor NJ; Genomics Core, Biosciences, Arizona State University, Tempe, Arizona 85281, United States., Buss K; Genomics Core, Biosciences, Arizona State University, Tempe, Arizona 85281, United States., Blain JM; Genomics Core, Biosciences, Arizona State University, Tempe, Arizona 85281, United States., Wagner CE; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Jurutka PW; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States., Marshall PA; School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts and Sciences, Arizona State University, Glendale, Arizona 85306, United States.
Jazyk:	angličtina
Zdroj:	ACS chemical neuroscience [ACS Chem Neurosci] 2024 Aug 07; Vol. 15 (15), pp. 2897-2915. Date of Electronic Publication: 2024 Jul 16.
DOI:	10.1021/acschemneuro.4c00286
Abstrakt:	Rexinoids are compounds that bind to the rexinoid X receptor (RXR) to modulate gene expression and have been proposed as a new class of therapeutics to treat Alzheimer's disease. Different rexinoids will initiate downstream effects that can be quite marked even though such compounds can be structurally similar and have comparable RXR binding affinities. RXR can both homo- and heterodimerize, and these protein-protein interactions and subsequent transactivating potential lead to differential gene expression, depending on the RXR dimeric partner, additional cofactors recruited, and downstream transcription factors that are up- or downregulated. Expression analysis was performed in the U87 human glioblastoma cell line treated with a panel of rexinoids, and our analysis demonstrated that rexinoids with similar RXR EC 50 values can have pronounced differences in differential gene expression. Rexinoid binding likely leads to distinctive RXR conformations that cause major downstream gene expression alterations via modulation of RXR interacting proteins. Yeast two-hybrid analysis of RXR bait with two RXR interacting partners demonstrates that rexinoids drive differential binding of RXR to distinctive protein partners. Physiochemical analysis of the rexinoids reveals that the molecules cluster similarly to their gene expression patterns. Thus, rexinoids with similar RXR binding affinities drive differential gene expression by stimulating additional binding patterns in RXR and its homo- and heteropartners, driven by the physicochemical characteristics of these molecules.
Databáze:	MEDLINE
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