Augereau Patrick, Badia Eric, Carascossa Sophie, Castet Audrey, Fritsch Samuel, Harmand Pierre-Olivier, Jalaguier Stéphan, Cavaillès Vincent
INSERM, U540, Montpellier, France.
Nucl Recept Signal. 2006 Oct 30;4:e024. doi: 10.1621/nrs.04024.
The nuclear receptor superfamily comprises ligand-regulated transcription factors that control various developmental and physiological pathways. These receptors share a common modular structure and regulate gene expression through the recruitment of a large set of coregulatory proteins. These transcription cofactors regulate, either positively or negatively, chromatin structure and transcription initiation. One of the first proteins to be identified as a hormone-recruited cofactor was RIP140. Despite its recruitment by agonist-liganded receptors, RIP140 exhibits a strong transcriptional repressive activity which involves several inhibitory domains and different effectors. Interestingly, the RIP140 gene, located on chromosome 21 in humans, is finely regulated at the transcriptional level by various nuclear receptors. In addition, the protein undergoes several post-translational modifications which control its repressive activity. Finally, experiments performed in mice devoid of the RIP140 gene indicate that this transcriptional cofactor is essential for female fertility and energy homeostasis. RIP140 therefore appears to be an important modulator of nuclear receptor activity which could play major roles in physiological processes and hormone-dependent diseases.
核受体超家族由控制各种发育和生理途径的配体调节转录因子组成。这些受体具有共同的模块化结构，并通过募集大量共调节蛋白来调节基因表达。这些转录辅因子正向或负向调节染色质结构和转录起始。最早被鉴定为激素募集辅因子的蛋白质之一是RIP140。尽管它被激动剂配体化的受体募集，但RIP140表现出强大的转录抑制活性，涉及几个抑制域和不同的效应器。有趣的是，位于人类21号染色体上的RIP140基因在转录水平上受到各种核受体的精细调节。此外，该蛋白质经历多种翻译后修饰，这些修饰控制其抑制活性。最后，在缺乏RIP140基因的小鼠中进行的实验表明，这种转录辅因子对雌性生育能力和能量稳态至关重要。因此，RIP140似乎是核受体活性的重要调节剂，可能在生理过程和激素依赖性疾病中发挥重要作用。
