| 저자(한글) |
Noh, Kyung Tae,Cha, Gil Sun,Kang, Tae Heung,Cho, Joon,Jung, In Duk,Kim, Kwang-Youn,Ahn, Soon-Cheol,You, Ji Chang,Park, Yeong-Min |
| 초록 |
Glycogen synthase kinase-3 beta; (GSK-3 beta;) is a serine/threonine protein kinase that is known to mediate cancer cell death. Here, we show that B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein, is regulated by GSK-3 beta; and that GSK-3 beta;-mediated regulation of Bcl-2 is crucial for mitochondrial-dependent cell death in paclitaxel-stimulated cells. We demonstrate that MCF7 GSK-3 beta; siRNA cells are more sensitive to cell death than MCF7 GFP control cells and that in the absence of GSK-3 beta;, Bcl-2 levels are reduced, a result enhanced by paclitaxel. Paclitaxel-induced JNK (c-Jun N-terminal kinase) activation is critical for Bcl-2 modulation. In the absence of GSK-3 beta;, Bcl-2 was unstable in an ubiquitination-dependent manner in both basal- and paclitaxel-treated cells. Furthermore, we demonstrate that GSK-3 beta;-mediated regulation of Bcl-2 influences cytochrome C release and mitochondrial membrane potential. Taken together, our data suggest that GSK-3 beta;-dependent regulation of Bcl-2 is crucial for mitochondria-dependent cell death in paclitaxel-mediated breast cancer therapy. [BMB Reports 2016; 49(1): 51-56] |
