Paul Bindu D, Shi Yun-Bo
Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bldg., Bethesda, MD 20892, USA.
Cell Res. 2003 Dec;13(6):459-64. doi: 10.1038/sj.cr.7290188.
The biological effects of thyroid hormone (T3) are mediated by the thyroid hormone receptor (TR). Amphibian metamorphosis is one of the most dramatic processes that are dependent on T3. T3 regulates a series of orchestrated developmental changes, which ultimately result in the conversion of an aquatic herbivorous tadpole to a terrestrial carnivorous frog. T3 is presumed to bind to TRs, which in turn recruit coactivators, leading to gene activation. The best-studied coactivators belong to the p160 or SRC family. Members of this family include SRC1/NCoA-1, SRC2/TIF2/GRIP1, and SRC3/pCIP/ACTR/AIB-1/RAC-3/TRAM-1. These SRCs interact directly with liganded TR and function as adapter molecules to recruit other coactivators such as p300/CBP. Here, we studied the expression patterns of these coactivators during various stages of development. Amongst the coactivators cloned in Xenopus laevis, SRC3 was found to be dramatically upregulated during natural and T3-induced metamorphosis, and SRC2 and p300 are expressed throughout postembryonic development with little change in their expression levels. These results support the view that these coactivators participate in gene regulation by TR during metamorphosis.
甲状腺激素（T3）的生物学效应由甲状腺激素受体（TR）介导。两栖动物变态是最依赖T3的显著过程之一。T3调节一系列精心编排的发育变化，最终导致水生草食性蝌蚪转变为陆生肉食性青蛙。推测T3与TR结合，进而招募共激活因子，导致基因激活。研究得最透彻的共激活因子属于p160或SRC家族。该家族成员包括SRC1/NCoA-1、SRC2/TIF2/GRIP1和SRC3/pCIP/ACTR/AIB-1/RAC-3/TRAM-1。这些SRC直接与配体化的TR相互作用，并作为衔接分子招募其他共激活因子，如p300/CBP。在此，我们研究了这些共激活因子在不同发育阶段的表达模式。在非洲爪蟾中克隆的共激活因子中，发现SRC3在自然变态和T3诱导的变态过程中显著上调，而SRC2和p300在胚胎后发育过程中均有表达，其表达水平变化不大。这些结果支持了这些共激活因子在变态过程中参与TR介导的基因调控的观点。
