转录辅抑制因子RIP140在代谢组织中的作用及机制

Role and molecular mechanism of transcriptional co-repressor RIP140 in metabolism tissue

核受体超家族在调节能量平衡过程中扮演重要角色。转录辅助调节因子通过募集一系列DNA或组蛋白结构修饰酶,调节核受体介导的靶基因转录。受体相互作用蛋白140(receptor-interacting protein140,RIP140)是一种转录辅抑制因子,其与核受体结合后能够负向调节多种代谢组织中靶基因的转录,包括脂肪组织、肌肉组织以及肝脏等。基因沉默RIP140后,多种代谢途径相关基因表达上调,主要涉及糖酵解、甘油三酯合成、三羧酸循环、脂肪酸β氧化、线粒体电子传递以及氧化磷酸化等能量代谢过程。RIP140有望成为治疗代谢综合征的候选靶点。

Nuclear receptors（NRs）superfamily signaling plays an important role in regulating the expression of gene involved inenergy homeostasis.The nuclear receptors regulate target gene expression through the recruitment of coregulatory proteins,which act as scaffolds or plateforms for linking NRs with enzyme complexes that modify DNA and histones.As a transcriptional co-repressor for NRs,RIP140 negatively regulates the transcription of target gene in metabolic tissue,such as adipose tissue,muscle and liver.In the absence of RIP140,genes expressions involved in metabolic pathways were upregulated including glycolysis,triglyceride synthesis,TCA cycle,fatty acid β oxidation,mitochondrial electron transport and oxidative phosphorylation.RIP140 may be a candidate therapeutic target for metabolism syndromes.