Institute of Molecular and Cell Biology, A STAR, Singapore 138673.
J Cell Sci. 2013 Jun 15;126(Pt 12):2740-6. doi: 10.1242/jcs.126367. Epub 2013 Apr 16.
Epithelial-mesenchymal transition (EMT) can be induced by several pleiotropically activated transcription factors, including the zinc-finger E-box-binding protein Zeb1. Mechanisms regulating Zeb1 expression have been partly uncovered, showing a critical role for the miR-200 family members. In the present study, we show that Zeb1 is regulated by the Arf GTPase-activating protein (GAP) Git2. Following the loss of Git2, we found that miR-146a maturation is enhanced, which in turn promotes the expression of Zeb1 and induction of EMT. Furthermore, we found that Cnot6L, a validated target of miR-146a, affects the stability of Zeb1 mRNA through its deadenylase activity. Our results present evidence for a new role for loss of Git2 in promoting EMT through a novel regulatory pathway.
上皮-间充质转化（EMT）可被多种多效激活的转录因子诱导，其中包括锌指 E 盒结合蛋白 Zeb1。调节 Zeb1 表达的机制已部分揭示，显示出 miR-200 家族成员的关键作用。在本研究中，我们表明 Zeb1 受 Arf GTP 酶激活蛋白（GAP）Git2 调节。在 Git2 缺失后，我们发现 miR-146a 的成熟增强，进而促进 Zeb1 的表达和 EMT 的诱导。此外，我们发现 Cnot6L，miR-146a 的一个验证靶标，通过其脱腺苷酸酶活性影响 Zeb1 mRNA 的稳定性。我们的结果为 Git2 缺失通过新的调节途径促进 EMT 提供了新的证据。
