Mechanisms and significance of nuclear receptor auto- and cross-regulation.

Mechanisms and significance of nuclear receptor auto- and cross-regulation.
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DOI:
10.1016/j.ygcen.2010.03.013
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发表时间:
2011-01-01
影响因子:
2.7
通讯作者:
Denver, Robert J.
Denver, Robert J.
中科院分区:
医学3区
文献类型:
--
作者:
Bagamasbad, Pia;Denver, Robert J.

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细胞表达的功能性激素受体的数量在很大程度上决定了其对激素信号的反应。因此,激素受体基因表达的调节是激素作用的核心组成部分。脊椎动物类固醇和甲状腺激素通过与核受体 (NR) 结合而发挥作用,核受体作为配体激活的转录因子。核受体基因受到多种相互作用的细胞内信号通路的调节。核受体配体可以调节介导激素作用(自动调节)的 NR 基因的表达,从而影响细胞对激素的反应。自身调节可以是正向的,也可以是负向的,激素分别增加或减少其自身 NR 的表达。在胚胎后发育和卵巢周期期间经常观察到积极的自动调节(自动诱导),它增强了细胞对激素信号的敏感性以驱动发育过程。相比之下,负性自动调节(自动抑制)对于青少年和成人的稳态负反馈反应可能变得很重要。除了自动调节之外,NR 还可以影响其他类型 NR 的表达(交叉调节),从而改变细胞对不同激素的反应方式。 NR 的交叉调节是暂时协调细胞对后续(不同)激素信号的反应或允许激素信号传导途径之间串扰的重要手段。
The number of functional hormone receptors expressed by a cell in large part determines its responsiveness to the hormonal signal. The regulation of hormone receptor gene expression is therefore a central component of hormone action. Vertebrate steroid and thyroid hormones act by binding to nuclear receptors (NR) that function as ligand-activated transcription factors. Nuclear receptor genes are regulated by diverse and interacting intracellular signaling pathways. Nuclear receptor ligands can regulate the expression of the gene for the NR that mediates the hormone's action (autoregulation), thus influencing how a cell responds to the hormone. Autoregulation can be either positive or negative, the hormone increasing or decreasing, respectively, the expression of its own NR. Positive autoregulation (autoinduction) is often observed during postembryoninc development, and during the ovarian cycle, where it enhances cellular sensitivity to the hormonal signal to drive the developmental process. By contrast, negative autoregulation (autorepression) may become important in the juvenile and adult for homeostatic negative feedback responses. In addition to autoregulation, a NR can influence the expression other types of NRs (cross-regulation), thus modifying how a cell responds to a different hormone. Cross-regulation by NRs is an important means to temporally coordinate cell responses to a subsequent (different) hormonal signal, or to allow for crosstalk between hormone signaling pathways.
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