转化生长因子β1通过在FaO肝癌细胞中以Smad3依赖的机制切割BAD来诱导细胞凋亡。
Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells.
作者信息
Kim Byung-Chul, Mamura Mizuko, Choi Kyeong Sook, Calabretta Bruno, Kim Seong-Jin
机构信息
Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892-50551, USA.
出版信息
Mol Cell Biol. 2002 Mar;22(5):1369-78. doi: 10.1128/MCB.22.5.1369-1378.2002.
Transforming growth factor beta (TGF-beta) induces apoptosis in a variety of cells. We have previously shown that TGF-beta 1 rapidly induces apoptosis in the FaO rat hepatoma cell line. We have now studied the effect of TGF-beta 1 on the expression of different members of the Bcl-2 family in these cells. We observed no detectable changes in the steady-state levels of Bcl-2, Bcl-X(L), and Bax. However, TGF-beta 1 induced caspase-dependent cleavage of BAD at its N terminus to generate a 15-kDa truncated protein. Overexpression of the 15-kDa truncated BAD protein enhanced TGF-beta 1-induced apoptosis, whereas a mutant BAD resistant to caspase 3 cleavage blocked TGF-beta 1-induced apoptosis. Overexpression of Smad3 dramatically enhanced TGF-beta 1-induced cleavage of BAD and apoptosis, whereas antisense Smad3 blocked TGF-beta 1-induced apoptosis and BAD cleavage. These results suggest that TGF-beta 1 induces apoptosis through the cleavage of BAD in a Smad3-dependent mechanism.
转化生长因子β（TGF-β）可诱导多种细胞发生凋亡。我们之前已表明，TGF-β1能迅速诱导FaO大鼠肝癌细胞系发生凋亡。我们现在研究了TGF-β1对这些细胞中Bcl-2家族不同成员表达的影响。我们观察到Bcl-2、Bcl-X(L)和Bax的稳态水平没有可检测到的变化。然而，TGF-β1诱导BAD在其N端发生半胱天冬酶依赖性切割，产生一个15 kDa的截短蛋白。15 kDa截短BAD蛋白的过表达增强了TGF-β1诱导的凋亡，而对半胱天冬酶3切割具有抗性的突变BAD则阻断了TGF-β1诱导的凋亡。Smad3的过表达显著增强了TGF-β1诱导的BAD切割和凋亡，而反义Smad3则阻断了TGF-β1诱导的凋亡和BAD切割。这些结果表明，TGF-β1通过依赖Smad3的机制切割BAD来诱导凋亡。
Zotero 插件