Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-α regulate transcriptional signaling and apoptosis
Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-α regulate transcriptional signaling and apoptosis
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DOI：
10.1074/jbc.m002547200
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发表时间：
2000-10-27
影响因子：
4.8
通讯作者：
Cohen, P
中科院分区：
文献类型：
--
作者：
Liu, BR;Lee, HY;Cohen, P
胰岛素样生长因子结合蛋白（IGFBP）-3以不依赖于IGF的方式调节细胞凋亡，并已被证明定位于细胞核。我们在酵母双杂交筛选中克隆了作为IGFBP-3蛋白伴侣的核受体维甲酸X受体-α>（*）over bar *（RXR-α）。多种方法显示IGFBP-3和RXR-α在细胞核内相互结合。IGFBP-3诱导的细胞凋亡在RXR-α敲除细胞中被消除。IGFBP-3和RXR配体在前列腺癌细胞中诱导凋亡中仅是添加剂。IGFBP-3增强RXR反应元件，抑制RARE信号。因此，RXR-α-IGFBP-3相互作用导致RXR-α转录活性的调节，并且对于介导IGFBP-3对细胞凋亡的作用是必不可少的。
Insulin-like growth factor-binding protein (IGFBP)-3 regulates apoptosis in an IGF-independent fashion and has been shown to localize to nuclei. We cloned the nuclear receptor retinoid X receptor-alpha>(*) over bar * (RXR-alpha) as an IGFBP-3 protein partner in a yeast two-hybrid screen. Multiple methodologies showed that IGFBP-3 and RXR-alpha bind each other within the nucleus. IGFBP-3-induced apoptosis was abolished in RXR-alpha -knockout cells. IGFBP-3 and RXR ligands mere additive in inducing apoptosis in prostate cancer cells. IGFBP-3 enhanced RXR response element and inhibited RARE signaling. Thus, RXR-alpha -IGFBP-3 interaction leads to modulation of the transcriptional activity of RXR-alpha and is essential for mediating the effects of IGFBP-3 on apoptosis.