- 著者
- Nakano Naoko Itoh Susumu Watanabe Yukihide Maeyama Kota Itoh Fumiko Kato Mitsuyasu
- 出版者
- American Society for Biochemistry and Molecular Biology
- 雑誌
- The journal of biological chemistry (ISSN:00219258)
- 巻号頁・発行日
- vol.285, no.49, pp.38023-38033, 2010-12
- 被引用文献数
- 43
The TGF-β and Wnt pathways are involved in cell fate and tumorigenicity. A recent report indicated that a TGF-β target gene, TMEPAI (transmembrane prostate androgen-induced RNA), is possibly also a downstream target of Wnt signaling. Although TMEPAI was believed to be involved in tumorigenicity because of its blockage of TGF-β signaling, how TGF-β and Wnt signals affect the activation of the TMEPAI gene is not well understood. Herein, we show that the TMEPAI promoter is regulated synergistically by TGF-β/Smad and Wnt/β-catenin/T cell factor (TCF) 7L2. The critical cis-element for dual signals, termed TGF-β-responsive TCF7L2-binding element (TTE), is located in intron 1 of the TMEPAI gene. TCF7L2, but not Smad proteins, bound to TTE, whereas the disruption of TTE by mutagenesis remarkably counteracted both TGF-β and TCF7L2 responses. The introduction of mutations in critical Smad-binding elements blocked the activation of the TMEPAI promoter by TCF7L2. Furthermore, our DNA-protein interaction experiments revealed the indirect binding of TCF7L2 to Smad-binding elements via Smad3 upon TGF-β stimulation as well as its TGF-β-dependent association with TTE. We demonstrate that the Wnt/β-catenin/TCF7L2 pathway is preferentially able to alter the transcriptional regulation of the TGF-β-target gene, TMEPAI.
- 著者
- Yang Weiwen Itoh Fumiko Ohya Hirotoshi Kishimoto Fukiko Tanaka Aya Nakano Naoko Itoh Susumu Kato Mitsuyasu
- 出版者
- Wiley-Blackwell
- 雑誌
- Cancer science (ISSN:13479032)
- 巻号頁・発行日
- vol.102, no.10, pp.1808-1814, 2011-10
- 被引用文献数
- 8 2
he basic helix–loop–helix protein E2-2 is known to play a role in quiescence of endothelial cells (ECs). However, it is unclear how the activity of E2-2 is controlled in the cells. In this study, we identified FAM96B as an interaction partner of E2-2. FAM96B interfered with E2-2-mediated effects on luciferase reporter activities. Furthermore, the suppression of vascular endothelial growth factor receptor 2 promoter activity by E2-2 was rescued by the expression of FAM96B in a dose-dependent manner. Interestingly, FAM96B decreased the expression of ectopic and endogenous E2-2 proteins. Mutational analysis revealed that the middle region of FAM96B is required for the limited expression of E2-2 protein. When FAM96B was expressed in ECs, the EC migration, proliferation, and tube formation were potentiated. Taken together, these findings suggest that FAM96B acts as a regulator of E2-2 through the control of its protein expression.