Hong Wei, Baniahmad Aria, Li Juan, Chang Chenglin, Gao Weizhen, Liu Yunde
Department of Laboratory Medicine, Tianjin Medical University, Tianjin, China.
FEBS Lett. 2009 Aug 6;583(15):2451-6. doi: 10.1016/j.febslet.2009.07.010. Epub 2009 Jul 15.
The Bcl-2 associated athanogene 1M (Bag-1M) is known to repress the transactivation of the glucocorticoid receptor (GR). We report here that Bag-1M inhibits the action of GR via recruitment of corepressors, including nuclear receptor corepressor (NcoR) and silencing mediator for retinoic acid and thyroid hormone receptor (SMRT), and histone deacetylase (HDAC)3 to the genomic response element of a glucocorticoid-regulated human metallothionein IIa (hMTIIa) gene. A mutant GR lacking the interaction with BAG-1M fails to recruit the corepressors NcoR and SMRT. RNAi-mediated knock down of corepressors and the use of HDAC inhibitor relieved Bag-1M-induced repression on the transactivation of the GR. In addition, Bag-1M is not involved in the degradation of the receptor. These findings indicate a novel mechanism by which Bag-1M acts as a corepressor and downregulates the activity of the GR.
已知Bcl-2相关抗凋亡基因1M（Bag-1M）可抑制糖皮质激素受体（GR）的反式激活。我们在此报告，Bag-1M通过招募共抑制因子抑制GR的作用，这些共抑制因子包括核受体共抑制因子（NcoR）、维甲酸和甲状腺激素受体沉默介质（SMRT）以及组蛋白去乙酰化酶（HDAC）3至糖皮质激素调节的人金属硫蛋白IIa（hMTIIa）基因的基因组反应元件。缺乏与BAG-1M相互作用的突变型GR无法招募共抑制因子NcoR和SMRT。RNA干扰介导的共抑制因子敲低以及HDAC抑制剂的使用减轻了Bag-1M诱导的对GR反式激活的抑制。此外，Bag-1M不参与受体的降解。这些发现表明了一种新机制，即Bag-1M作为共抑制因子并下调GR的活性。
