首页> 外文期刊>Molecular and Cellular Biology >Cyclin D1 and C/EBPβ LAP1 Operate in a Common Pathway To Promote Mammary Epithelial Cell Differentiation
【24h】

Cyclin D1 and C/EBPβ LAP1 Operate in a Common Pathway To Promote Mammary Epithelial Cell Differentiation

机译:细胞周期蛋白D1和C /EBPβLAP1在促进乳腺上皮细胞分化的共同途径中运作。

获取原文
           

摘要

Both cyclin D1 and the transcription factor C/EBPβ are required for mammary epithelial cell differentiation; however, the pathway in which they operate is uncertain. Previous analyses of the patterns of gene expression in human tumors suggested a connection between cyclin D1 overexpression and C/EBPβ, but whether this represents a cancer-specific gain of function for cyclin D1 is unknown. C/EBPβ is an intronless gene encoding three protein isoforms—LAP1, LAP2, and LIP. Here, we provide evidence that cyclin D1 engages C/EBPβ in an isoform-specific manner. Cyclin D1 binds to LAP1, an event that activates the transcriptional function of LAP1 by relieving its autoinhibited state effected by intramolecular interactions. Reexpression of LAP1 but not LAP2 or LIP restores the ability of C/EBPβ-deficient mammary epithelial cells to differentiate and does so in a manner dependent on cyclin D1. And cyclin D1-mediated activation of LAP1 participates in mammary epithelial cell differentiation. Our findings indicate that cyclin D1 and C/EBPβ LAP1 operate in a common pathway to promote mammary epithelial cell differentiation.
机译:乳腺上皮细胞分化需要细胞周期蛋白D1和转录因子C /EBPβ。但是,他们运作的途径尚不确定。先前对人类肿瘤中基因表达模式的分析表明,细胞周期蛋白D1过表达与C /EBPβ之间存在联系,但未知这是否代表细胞周期蛋白D1的癌症特异性功能增强。 C / EBP β是一个无内含子基因,编码三种蛋白质同工型:LAP1,LAP2和LIP。在这里,我们提供了细胞周期蛋白D1以同工型特异性方式参与C /EBPβ的证据。细胞周期蛋白D1与LAP1结合,该事件通过缓解分子内相互作用影响的LAP1自抑制状态来激活LAP1的转录功能。 LAP1而非LAP2或LIP的重新表达恢复了 C / EBP β缺陷型乳腺上皮细胞的分化能力,并依赖于细胞周期蛋白D1。细胞周期蛋白D1介导的LAP1的激活参与了乳腺上皮细胞的分化。我们的发现表明,细胞周期蛋白D1和C /EBPβLAP1以共同的途径促进乳腺上皮细胞分化。

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