...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Cellular Physiology >Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21(WAF1/Cip1).
【24h】

Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21(WAF1/Cip1).

机译：Smad pathway-specific转录调控p21的细胞周期抑制剂(WAF1 / Cip1)。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Transforming growth factor-beta (TGF-beta) inhibits epithelial cell growth, in part via transcriptional induction of the cell cycle inhibitor p21(WAF1/Cip1) (p21). We show that bone morphogenetic protein (BMP)-7 induces higher p21 expression than TGF-beta1 in various epithelial cells. Despite this, BMP-7 only weakly suppresses epithelial cell proliferation, as Id2, a cell cycle-promoting factor, becomes concomitantly induced by BMP-7. Signaling studies with all type I receptors of the TGF-beta superfamily show that BMP receptors induce higher p21 expression than TGF-beta/activin receptors. Smad4 is essential for p21 regulation by all receptor pathways. Based on the previously known ability of c-Myc to block p21 expression and epithelial growth arrest in response to TGF-beta1, we demonstrate that ectopic c-Myc expression can abrogate Smad-mediated p21 induction by all TGF-beta and BMP receptors. Furthermore, p21 induction by all receptor pathways can be blocked by the natural inhibitors of the TGF-beta superfamily. Smad7 inhibits all pathways whereas Smad6 selectively inhibits the BMP pathways. The observed pathway specificity reflects the efficiency by which BMP Smads, compared to TGF-beta Smads, transactivate the p21 promoter. In addition, BMP-specific Smads, Smad1, Smad5, and especially Smad8, induce endogenous p21 mRNA and protein levels, while they fail to induce epithelial growth inhibition when compared to TGF-beta receptor-phosphorylated Smads (R-Smads), Smad2 and Smad3. Thus, p21 is a common target of all TGF-beta superfamily pathways. However, the ability of TGF-beta superfamily members to induce cell growth arrest depends on the regulation of additional gene targets.
机译：转化生长因子(及)抑制上皮细胞生长,部分通过转录诱导的细胞周期p21抑制剂(WAF1 / Cip1) (p21)。形态蛋白(BMP) 7 p21诱发高表达比TGF-beta1各种上皮细胞。Id2下上皮细胞增殖,细胞cycle-promoting因素,与此同时BMP-7引起的。我的受体及总科显示骨形态发生蛋白受体诱导p21的表达高于鉴定及/激活素受体。p21监管所有受体途径。根据之前所知的原癌基因的能力块p21表达与上皮生长被捕为了应对TGF-beta1,我们证明异位原癌基因表达可以废除及和p21 Smad-mediated感应骨形态发生蛋白受体。受体通路可以被自然抑制剂的鉴定及总科。抑制所有通路而Smad6选择性抑制了BMP通路。骨形态发生蛋白的特异性反映了效率相比,Smads及Smads transactivatep21启动子。Smads、Smad1 Smad5,特别是Smad8诱导内源性p21 mRNA和蛋白水平,而他们不能诱导上皮生长抑制相比及receptor-phosphorylatedSmads (R-Smads) Smad2 Smad3。共同目标及总科通路。总科成员诱导细胞生长被捕取决于其他基因的调控目标。

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