Characterization of a novel compound that promotes myogenesis via Akt and transcriptional co-activator with PDZ-binding motif (TAZ) in mouse C2C12 cells

通过 Akt 和具有 PDZ 结合基序 (TAZ) 的转录共激活因子促进小鼠 C2C12 细胞中肌肉生成的新型化合物的表征

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作者:Manami Kodaka, Fengju Mao, Kyoko Arimoto-Matsuzaki, Masami Kitamura, Xiaoyin Xu, Zeyu Yang, Kentaro Nakagawa, Junichi Maruyama, Kana Ishii, Chihiro Akazawa, Takuya Oyaizu, Naoki Yamamoto, Mari Ishigami-Yuasa, Nozomi Tsuemoto, Shigeru Ito, Hiroyuki Kagechika, Hiroshi Nishina, Yutaka Hata

Abstract

Transcriptional co-activator with PDZ-binding motif (TAZ) plays versatile roles in the regulation of cell proliferation and differentiation. TAZ activity changes in response to the cellular environment such as mechanic and nutritional stimuli, osmolarity, and hypoxia. To understand the physiological roles of TAZ, chemical compounds that activate TAZ in cells are useful as experimental reagents. Kaempferol, TM-25659, and ethacridine are reported as TAZ activators. However, as each TAZ activator has a distinct property in cellular functions, additional TAZ activators are awaiting. We screened for TAZ activators and previously reported IB008738 as a TAZ activator that promotes myogenesis in C2C12 cells. In this study, we have characterized IBS004735 that was obtained in the same screening. IBS004735 also promotes myogenesis in C2C12 cells, but is not similar to IBS008738 in the structure. IBS004735 activates TAZ via Akt and has no effect on TAZ phosphorylation, which is the well-described key modification to regulate TAZ activity. Thus, we introduce IBS004735 as a novel TAZ activator that regulates TAZ in a yet unidentified mechanism.

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