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- Title
A Pleiotropic Role for the Orphan Nuclear Receptor Small Heterodimer Partner in Lipid Homeostasis and Metabolic Pathways.
- Authors
Garruti, Gabriella; Wang, Helen H.; Bonfrate, Leonilde; de Bari, Ornella; Wang, David Q.-H.; Portincasa, Piero
- 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 DNAbinding domain but contains a putative ligand-binding domain. SHP is a transcriptional regulator affectingmultiple 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.
- Subjects
NUCLEAR receptors (Biochemistry); MULTIDRUG resistance; HOMEOSTASIS; PHYSIOLOGICAL effects of lipids; GENETIC transcription; METABOLIC disorders; TARGETED drug delivery
- Publication
Journal of Lipids, 2012, p1
- ISSN
2090-3030
- Publication type
Article
- DOI
10.1155/2012/304292