Goodman Cancer Centre, McGill University, Montréal, Québec, Canada.
Genes Dev. 2010 Mar 15;24(6):537-42. doi: 10.1101/gad.1871610. Epub 2010 Mar 1.
Estrogen-related receptor alpha (ERRalpha) and proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) play central roles in the transcriptional control of energy homeostasis, but little is known about factors regulating their activity. Here we identified the homeobox protein prospero-related homeobox 1 (Prox1) as one such factor. Prox1 interacts with ERRalpha and PGC-1alpha, occupies promoters of metabolic genes on a genome-wide scale, and inhibits the activity of the ERRalpha/PGC-1alpha complex. DNA motif analysis suggests that Prox1 interacts with the genome through tethering to ERRalpha and other factors. Importantly, ablation of Prox1 and ERRalpha have opposite effects on the respiratory capacity of liver cells, revealing an unexpected role for Prox1 in the control of energy homeostasis.
雌激素相关受体α（ERRα）和过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC-1α）在能量稳态的转录调控中发挥核心作用，但关于调节它们活性的因素知之甚少。在这里，我们鉴定了同源盒蛋白prospero 相关同源盒 1（Prox1）作为这样的因素之一。Prox1 与 ERRα 和 PGC-1α 相互作用，在全基因组范围内占据代谢基因的启动子，并抑制 ERRα/PGC-1α 复合物的活性。DNA 基序分析表明，Prox1 通过与 ERRα 和其他因子的连接与基因组相互作用。重要的是，Prox1 和 ERRα 的缺失对肝细胞的呼吸能力有相反的影响，这揭示了 Prox1 在能量稳态控制中的一个意外作用。
