Nuclear receptor coregulators: modulators of pathology and therapeutic targets.
Nuclear receptor coregulators: modulators of pathology and therapeutic targets.
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DOI：
10.1038/nrendo.2012.100
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发表时间：
2012-10
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核受体超家族包括与类固醇、甲状腺和类维生素A激素和其他配体结合的转录因子。到目前为止，在文献中已经报道了超过350种辅助调节因子，并且辅助调节因子蛋白复合物的蛋白质组学分析的进展已经揭示了还存在更多数量的辅助调节因子相互作用蛋白。辅调节因子功能障碍与多种病理状态、遗传综合征和癌症有关。与正常辅调节因子功能破坏相关的疾病的标志是对动物生理学的多效性效应，其通常表现为代谢和神经系统的失调。辅调节因子具有广泛的生理和病理功能，使其成为治疗依赖性癌症等疾病的有希望的新药物靶点。在蛋白质组学，基因组学和转录组学的进展提供了新的见解，在系统范围内的生物学coregulators，并将导致如何coregulators可以在复杂和多方面的遗传因素，激素，饮食，环境和压力的背景下进行评估的新的理解。最终，更好地了解存在于辅助调节器功能和人类疾病之间的关联有望扩大未来辅助调节器靶向药物的使用适应症。
The nuclear receptor superfamily includes transcription factors that transduce steroid, thyroid and retinoid hormones and other ligands in conjunction with coregulators. To date, over 350 coregulators have been reported in the literature, and advances in proteomic analyses of coregulator protein complexes have revealed that a far greater number of coregulator-interacting proteins also exist. Coregulator dysfunction has been implicated in diverse pathological states, genetic syndromes and cancer. A hallmark of disease related to the disruption of normal coregulator function is the pleiotropic effect on animal physiology, which is frequently manifested as the dysregulation of metabolic and neurological systems. Coregulators have broad physiological and pathological functions that make them promising new drug targets for diseases such as hormone-dependent cancers. Advances in proteomics, genomics and transcriptomics have provided novel insights into the biology of coregulators at a system-wide level and will lead the way to a new understanding of how coregulators can be evaluated in the context of complex and multifaceted genetic factors, hormones, diet, the environment and stress. Ultimately, better knowledge of the associations that exist between coregulator function and human diseases is expected to expand the indications for the use of future coregulator-targeted drugs.