TGF-β1에 의해 유도되는 세포사멸 신호전달 과정에서 Rac1 GTPase의 역할 규명

  Transforming growth factor (TGF) β1 is a potent inducer of apoptosis in the liver. Recently, c-jun NH₂-terminal kinase (JNK) was shown to be involved in signal transduction in response to TGF-β1. However, the detailed mechanism of TGF-β1-mediated signaling of apoptosis remains largely unknown. In the present study, we investigated the role of Rac1, a member of Rho family GTPases, in the TGF-β1-induced apoptosis of FaO hepatoma cells. Our results showed that TGF-β1-induced apoptosis detected by propidium iodide staining and caspase activation, was significantly blocked in FaO-Rac1N17 cells expressing a dominant negative Rac1 mutant, suggesting a crucial role for Rac1 in TGF-β1 signaling to apoptosis. In addition, we found that TGF-β 1 induced the activation of JNK in a Rac-dependent manner. It thus appears that Rac1 acts upstream of JNK, and that a Rac1-JNK -dependent cascade mediates the TGF-β1-induced apoptosis of FaO cells.