Smad 信号通路与叉头框蛋白信号通路在调控神经上皮细胞和胶质母细胞瘤细胞增殖中的整合作用

Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.

作者信息

Seoane Joan, Le Hong-Van, Shen Lijian, Anderson Stewart A, Massagué Joan

机构信息

Cancer Biology and Genetics Program and Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, 1300 York Avenue, New York, NY 1002, USA.

出版信息

Cell. 2004 Apr 16;117(2):211-23. doi: 10.1016/s0092-8674(04)00298-3.

DOI:10.1016/s0092-8674(04)00298-3

PMID:15084259

Abstract

FoxO Forkhead transcription factors are shown here to act as signal transducers at the confluence of Smad, PI3K, and FoxG1 pathways. Smad proteins activated by TGF-beta form a complex with FoxO proteins to turn on the growth inhibitory gene p21Cip1. This process is negatively controlled by the PI3K pathway, a known inhibitor of FoxO localization in the nucleus, and by the telencephalic development factor FoxG1, which we show binds to FoxO-Smad complexes and blocks p21Cip1 expression. We suggest that the activity of this network confers resistance to TGF-beta-mediated cytostasis during the development of the telencephalic neuroepithelium and in glioblastoma brain tumor cells.

摘要

本文显示，FoxO叉头转录因子在Smad、PI3K和FoxG1信号通路的交汇处作为信号转导分子发挥作用。由转化生长因子β（TGF-β）激活的Smad蛋白与FoxO蛋白形成复合物，从而开启生长抑制基因p21Cip1。这一过程受到PI3K信号通路（一种已知的抑制FoxO在细胞核中定位的因子）以及端脑发育因子FoxG1的负调控，我们的研究表明，FoxG1可与FoxO-Smad复合物结合并阻断p21Cip1的表达。我们认为，在端脑神经上皮发育过程以及胶质母细胞瘤脑肿瘤细胞中，该信号网络的活性赋予了对TGF-β介导的细胞生长停滞的抗性。