首页> 外文期刊>Molecular and Cellular Biology >RORα Binds to E2F1 To Inhibit Cell Proliferation and Regulate Mammary Gland Branching Morphogenesis
【24h】

RORα Binds to E2F1 To Inhibit Cell Proliferation and Regulate Mammary Gland Branching Morphogenesis

机译:RORα绑定到E2F1抑制细胞增殖并调节乳腺分支形态发生

获取原文
           

摘要

Retinoic acid receptor-related orphan nuclear receptor alpha (RORα) is a potent tumor suppressor that reduces cell proliferation and inhibits tumor growth. However, the molecular mechanism by which it inhibits cell proliferation remains unknown. We demonstrate a noncanonical nuclear receptor pathway in which RORα binds to E2F1 to inhibit cell cycle progression. We showed that RORα bound to the heptad repeat and marked box region of E2F1 and suppressed E2F1-regulated transcription in epithelial cells. Binding of RORα inhibited E2F1 acetylation and its DNA-binding activity by recruiting histone deacetylase 1 (HDAC1) to the protein complexes. Knockdown of HDAC1 or inhibition of HDAC activity at least partially rescued transcription factor activity of E2F1 that was repressed by RORα. Importantly, RORα levels were increased in mammary ducts compared to terminal end buds and inversely correlated with expression of E2F1 target genes and cell proliferation. Silencing RORα in mammary epithelial cells significantly enhanced cell proliferation in the ductal epithelial cells and promoted side branching of the mammary ducts. These results reveal a novel link between RORα and E2F1 in regulating cell cycle progression and mammary tissue morphogenesis.
机译:维甲酸受体相关的孤儿核受体α(RORα)是有效的肿瘤抑制因子,可减少细胞增殖并抑制肿瘤生长。然而,其抑制细胞增殖的分子机制仍然未知。我们证明了其中RORα绑定到E2F1抑制细胞周期进程的非规范核受体途径。我们显示RORα绑定到七联重复和E2F1的标记框区域,并抑制上皮细胞中E2F1调节的转录。通过将组蛋白脱乙酰基酶1(HDAC1)募集到蛋白质复合物中,RORα的结合抑制了E2F1乙酰化及其DNA结合活性。抑制HDAC1或抑制HDAC活性至少部分挽救了被RORα抑制的E2F1转录因子活性。重要的是,与末端芽相比,乳腺导管中的RORα水平升高,并且与E2F1靶基因的表达和细胞增殖成反比。沉默乳腺上皮细胞中的RORα显着增强了导管上皮细胞中的细胞增殖并促进了乳腺导管的侧分支。这些结果揭示了RORα和E2F1之间在调节细胞周期进程和乳腺组织形态发生中的新颖联系。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号