Knoedler Joseph R, Denver Robert J
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109-1048, USA; Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Gen Comp Endocrinol. 2014 Jul 1;203:49-59. doi: 10.1016/j.ygcen.2014.03.003. Epub 2014 Mar 15.
Binding of steroid and thyroid hormones to their cognate nuclear receptors (NRs) impacts virtually every aspect of postembryonic development, physiology and behavior, and inappropriate signaling by NRs may contribute to disease. While NRs regulate genes by direct binding to hormone response elements in the genome, their actions may depend on the activity of other transcription factors (TFs) that may or may not bind DNA. The Krüppel-like family of transcription factors (KLF) is an evolutionarily conserved class of DNA-binding proteins that influence many aspects of development and physiology. Several members of this family have been shown to play diverse roles in NR signaling. For example, KLFs (1) act as accessory transcription factors for NR actions, (2) regulate expression of NR genes, and (3) as gene products of primary NR response genes function as key players in NR-dependent transcriptional networks. In mouse models, deletion of different KLFs leads to aberrant transcriptional and physiological responses to hormones, underscoring the importance of these proteins in the regulation of hormonal signaling. Understanding the functional relationships between NRs and KLFs will yield important insights into mechanisms of NR signaling. In this review we present a conceptual framework for understanding how KLFs participate in NR signaling, and we provide examples of how these proteins function to effect hormone action.
类固醇和甲状腺激素与其同源核受体（NRs）的结合几乎影响胚胎后发育、生理和行为的方方面面，而NRs的信号传导异常可能会引发疾病。虽然NRs通过直接结合基因组中的激素反应元件来调控基因，但其作用可能取决于其他转录因子（TFs）的活性，这些转录因子可能结合也可能不结合DNA。Krüppel样转录因子家族（KLF）是一类在进化上保守的DNA结合蛋白，影响发育和生理的许多方面。该家族的几个成员已被证明在NR信号传导中发挥多种作用。例如，KLFs（1）作为NR作用的辅助转录因子，（2）调节NR基因的表达，以及（3）作为初级NR反应基因的基因产物，在NR依赖性转录网络中起关键作用。在小鼠模型中，不同KLFs的缺失会导致对激素的异常转录和生理反应，突显了这些蛋白质在激素信号调节中的重要性。了解NRs和KLFs之间的功能关系将为NR信号传导机制提供重要见解。在本综述中，我们提出了一个概念框架，以理解KLFs如何参与NR信号传导，并提供这些蛋白质如何发挥作用以影响激素作用的实例。
