De Degejing, Chen Apeng, Wu Zhiqiang, Lv Songya, He Guoqing, Qi Yipeng
The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, PR China.
Biol Chem. 2009 Feb;390(2):157-65. doi: 10.1515/BC.2009.014.
Pygopus, a very important component of the Wnt signaling transcriptional complex, has multiple functions in both Wnt-dependent and -independent pathways. Human Pygopus2 (Pygo2) is expressed in many cancers and plays an important role in tumor growth. In the present study, we generated human carcinoma (HeLa) cell lines stably expressing Pygo2, which counteracts vinblastine- induced apoptosis. The anti-apoptotic function was determined by DNA fragmentation, sub-G1 appearance, loss of mitochondrial membrane potential (Deltapsim) and the activation of caspase-9 and caspase-3. In addition, we found that Pygo2 effectively blocks vinblastineinduced c-Jun and AP-1 activation, maintains the anti-apoptotic protein Bcl-2 in an unphosphorylated state, and thus can render cells resistant to apoptosis. However, Pygo2 does not alter the vinblastine-induced cell cycle changes. Here, we describe an anti-apoptotic activity exerted by Pygo2 through blocking activation of the JNK/AP-1 signaling pathway induced by vinblastine.
Pygo蛋白是Wnt信号转录复合物的一个非常重要的组成部分，在Wnt依赖和非依赖途径中都具有多种功能。人类Pygopus2（Pygo2）在许多癌症中表达，并在肿瘤生长中发挥重要作用。在本研究中，我们构建了稳定表达Pygo2的人癌细胞系（HeLa），该细胞系可对抗长春碱诱导的细胞凋亡。通过DNA片段化、亚G1期出现、线粒体膜电位丧失（Δψm）以及半胱天冬酶-9和半胱天冬酶-3的激活来确定其抗凋亡功能。此外，我们发现Pygo2能有效阻断长春碱诱导的c-Jun和AP-1激活，使抗凋亡蛋白Bcl-2维持在未磷酸化状态，从而使细胞对凋亡产生抗性。然而，Pygo2不会改变长春碱诱导的细胞周期变化。在此，我们描述了Pygo2通过阻断长春碱诱导的JNK/AP-1信号通路激活所发挥的抗凋亡活性。
