A pleiotropic role for the orphan nuclear receptor small heterodimer partner in lipid homeostasis and metabolic pathways.
A pleiotropic role for the orphan nuclear receptor small heterodimer partner in lipid homeostasis and metabolic pathways.
复制标题
DOI：
10.1155/2012/304292
复制
发表时间：
2012
影响因子：
5.3
通讯作者：
Portincasa P
中科院分区：
文献类型：
--
作者：
Garruti G;Wang HH;Bonfrate L;de Bari O;Wang DQ;Portincasa P
核受体（Nuclear receptor，NR）是代谢性疾病中最丰富的一类转录调节因子，已成为有前途的药物靶点。小异源二聚体伴侣（SHP; NR 0 B2）是一种独特的孤儿NR，缺乏DNA结合结构域，但含有一个推定的配体结合结构域。SHP是一种转录调节因子，影响多种关键生物学功能和代谢过程，包括胆固醇、胆汁酸和脂肪酸代谢，以及生殖生物学和葡萄糖-能量稳态。大约一半的哺乳动物核受体和几种转录辅助调节因子可以与SHP相互作用。SHP介导的靶转录因子的抑制至少包括三种机制，包括直接干扰NR的C-末端激活功能2（AF 2）辅激活子结构域、辅抑制子的募集或与NR/转录因子表面的直接相互作用。未来的研究必须集中在合成配体作为一系列代谢异常的潜在治疗靶点作用于SHP。目前的理解SHP的多效性的作用，本文进行了检查，并与SHP功能的主要代谢方面也将进行讨论。
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.
登录
查看更多内容
影响因子：
14.9
作者：
Chanda D;Xie YB;Choi HS
通讯作者：
Choi HS
影响因子：
3.5
作者：
Cao, HN;Hegele, RA
通讯作者：
Hegele, RA
影响因子：
3.9
作者：
Enya, Mayumi;Horikawa, Yukio;Takeda, Jun
通讯作者：
Takeda, Jun
影响因子：
14.9
作者：
Boulias, K;Talianidis, I
通讯作者：
Talianidis, I
影响因子：
64.5
作者：
Bookout, Angie L.;Jeong, Yangsik;Mangelsdorf, David J.
通讯作者：
Mangelsdorf, David J.