Deblois Geneviève, Giguère Vincent
Goodman Cancer Research Centre, McGill University, Montréal, Québec, Canada, H3A 1A3.
Biochim Biophys Acta. 2011 Aug;1812(8):1032-40. doi: 10.1016/j.bbadis.2010.12.009. Epub 2010 Dec 21.
Orphan nuclear receptors, in a manner comparable to classic steroid hormone receptors, regulate key developmental and physiological processes. However, the lack of appropriate pharmacological tools has often hindered the identification and study of their biological functions. In this review, we demonstrate that functional and physiological genomics are effective alternatives to discover biological functions associated with orphan nuclear receptors. Indeed, we document that these approaches have allowed for the unambiguous identification of the estrogen-related receptors (ERRs) α, β, and γ (NR3B1, 2, and 3) as global regulators of cellular energy metabolism. We further show that although the three ERR isoforms control analogous gene networks, each isoform performs unique biological functions in a tissue-specific manner in response to a variety of physiological stressors. Finally, we discuss how the activity of the three ERR isoforms contributes to the development and progression of metabolic diseases as well as to the adaptation of cancer cells to their unique bioenergetic requirement. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
孤儿核受体以一种与经典甾体激素受体类似的方式，调节关键的发育和生理过程。然而，缺乏合适的药理学工具常常阻碍了对其生物学功能的鉴定和研究。在本综述中，我们证明功能和生理基因组学是发现与孤儿核受体相关生物学功能的有效替代方法。事实上，我们记录了这些方法已明确鉴定出雌激素相关受体（ERRs）α、β和γ（NR3B1、2和3）作为细胞能量代谢的全局调节因子。我们进一步表明，尽管这三种ERR异构体控制类似的基因网络，但每种异构体在响应各种生理应激源时，以组织特异性方式执行独特的生物学功能。最后，我们讨论这三种ERR异构体的活性如何促进代谢疾病的发展和进展，以及癌细胞如何适应其独特的生物能量需求。本文是名为：“将核受体从健康转化为疾病”的特刊的一部分。
