MDM2 通过与 HeLa 细胞中 Itch 的相互作用促进 p73 的蛋白酶体降解。
MDM2 promotes the proteasomal degradation of p73 through the interaction with Itch in HeLa cells.
机构信息
Laboratory of Anti-tumor Research, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
出版信息
Biochem Biophys Res Commun. 2010 Dec 17;403(3-4):405-11. doi: 10.1016/j.bbrc.2010.11.043. Epub 2010 Nov 17.
It has been shown that MDM2 inhibits the transcriptional and pro-apoptotic activities of p73 but does not promote its proteasomal degradation. In this study, we found that MDM2 indirectly induces the degradation of p73 through the interaction with Itch in HeLa cells. During adriamycin (ADR)-mediated apoptosis, p53 and p73 were induced to stabilize in association with a significant reduction of MDM2 and Itch, suggesting that, in addition to Itch, MDM2 could also be involved in the stability control of p73. As expected, forced expression of MDM2 resulted in a remarkable reduction of p73. MDM2-mediated degradation of p73 was inhibited by MG-132. Intriguingly, siRNA-mediated knockdown of Itch significantly attenuated the negative effect of MDM2 on p73. Additionally, MDM2 bound to Itch in HeLa cells but not in H1299 cells. Collectively, our present findings suggest that MDM2 promotes Itch-mediated degradation of p73 through the interaction with Itch in HeLa cells.
已经表明，MDM2 抑制 p73 的转录和促凋亡活性，但不促进其蛋白酶体降解。在这项研究中，我们发现 MDM2 通过与 HeLa 细胞中的 Itch 相互作用，间接诱导 p73 的降解。在阿霉素（ADR）介导的细胞凋亡过程中，p53 和 p73 被诱导稳定，同时 MDM2 和 Itch 的表达显著减少，表明除了 Itch 之外，MDM2 还可能参与 p73 的稳定性控制。正如预期的那样，强制表达 MDM2 导致 p73 的显著减少。MG-132 抑制了 MDM2 介导的 p73 降解。有趣的是，siRNA 介导的 Itch 敲低显著减弱了 MDM2 对 p73 的负效应。此外，MDM2 与 HeLa 细胞中的 Itch 结合，但不与 H1299 细胞结合。总之，我们目前的研究结果表明，MDM2 通过与 HeLa 细胞中的 Itch 相互作用，促进 Itch 介导的 p73 降解。
Zotero 插件