A pleiotropic role for the orphan nuclear receptor small heterodimer partner in lipid homeostasis and metabolic pathways.

Journal of Lipids
Gabriella GarrutiPiero Portincasa

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.

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Citations

Nov 6, 2014·The Journal of Endocrinology·Gabriel Forn-CuníBeatriz Novoa
Oct 28, 2015·Nuclear Receptor Research·An ZouYuxia Zhang
Oct 23, 2018·F1000Research·Agostino Di Ciaula, Piero Portincasa
Mar 23, 2018·Cancer Biomarkers : Section a of Disease Markers·Maryam KhorasaniReza Mahdian
Aug 23, 2020·Journal of Clinical Medicine·Agostino Di CiaulaPiero Portincasa
Jan 15, 2021·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Sudhir KumarRakesh K Tyagi
Mar 27, 2021·Endocrinology·James T NguyenSayeepriyadarshini Anakk

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Methods Mentioned

BETA
immunoprecipitation

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