Gyeong-Gi Bio Center, Suwon, Korea.
Amino Acids. 2011 Mar;40(3):885-93. doi: 10.1007/s00726-010-0719-8. Epub 2010 Sep 8.
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAc addition to numerous cellular proteins including transcription and nuclear pore complexes and plays a key role in cellular signaling. One differentially spliced isoform of OGT is normally targeted to mitochondria (mOGT) but is quite cytotoxic when expressed in cells compared with the ncOGT isoform. To understand the basis of this selective cytotoxicity, we constructed a fully functional ecdysone-inducible GFP-OGT. Elevated GFP-OGT expression induced a dramatic increase in intracellular O-GlcNAcylated proteins. Furthermore, enhanced OGT expression efficiently triggered programmed cell death. Apoptosis was dependent upon the unique N-terminus of mOGT, and its catalytic activity. Induction of mOGT expression triggered programmed cell death in every cell type tested including INS-1, an insulin-secreting cell line. These studies suggest that deregulated activity of the mitochondrially targeted mOGT may play a role in triggering the programmed cell death observed with diseases such as diabetes mellitus and neurodegeneration.
O-连接的 N-乙酰葡萄糖胺转移酶（OGT）催化 O-GlcNAc 向包括转录和核孔复合物在内的许多细胞蛋白的添加，并在细胞信号转导中发挥关键作用。OGT 的一种差异剪接同工型通常靶向线粒体（mOGT），但与 ncOGT 同工型相比，在细胞中表达时具有相当的细胞毒性。为了了解这种选择性细胞毒性的基础，我们构建了一个完全功能性的蜕皮激素诱导 GFP-OGT。GFP-OGT 表达的增加诱导了细胞内 O-GlcNAc 化蛋白的显著增加。此外，增强的 OGT 表达有效地引发了程序性细胞死亡。细胞凋亡依赖于 mOGT 的独特 N 端及其催化活性。mOGT 表达的诱导在包括 INS-1（一种胰岛素分泌细胞系）在内的每一种测试的细胞类型中都触发了程序性细胞死亡。这些研究表明，靶向线粒体的 mOGT 的活性失调可能在触发糖尿病和神经退行性疾病等疾病中观察到的程序性细胞死亡中发挥作用。
