A Pleiotropic Role for the Orphan Nuclear Receptor Small Heterodimer Partner in Lipid Homeostasis and Metabolic Pathways. (22nd April 2012)

• Record Type: Journal Article
• Authors: Garruti, Gabriella; Wang, Helen H.; Bonfrate, Leonilde; de Bari, Ornella; Wang, David Q.-H.; Portincasa, Piero
• Other Names: Neuschwander-Tetri B. A. Academic Editor.
• Is Part Of: Journal of lipids. Volume 2012(2012)
• Publication Date: 2012-04-22
• Subjects: Lipids -- Periodicals; Lipids; Lipids; Electronic journals; Periodicals; Periodicals; 572.57
• DOI: 10.1155/2012/304292
• Languages: English
• ISSNs: 2090-3030

Abstract

Abstract : Nuclear receptors (NRs) comprise one of the most abundant classes of transcriptional regulators of metabolic diseases and have emerged as promising pharmaceutical targets. Small heterodimer partner (SHP; NR0B2) is a unique orphan NR lacking a DNA-binding domain but contains a putative ligand-binding domain. SHP is a transcriptional regulator affecting multiple key biological functions and metabolic processes including cholesterol, bile acid, and fatty acid metabolism, as well as reproductive biology and glucose-energy homeostasis. About half of all mammalian NRs and several transcriptional coregulators can interact with SHP. The SHP-mediated repression of target transcription factors includes at least three mechanisms including direct interference with the C-terminal activation function 2 (AF2) coactivator domains of NRs, recruitment of corepressors, or direct interaction with the surface of NR/transcription factors. Future research must focus on synthetic ligands acting on SHP as a potential therapeutic target in a series of metabolic abnormalities. Current understanding about the pleiotropic role of SHP is examined in this paper, and principal metabolic aspects connected with SHP function will be also discussed.