Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Korea.
J Biol Chem. 2010 Aug 13;285(33):25500-5. doi: 10.1074/jbc.M109.091413. Epub 2010 Jun 17.
Gadd45b has been known as a positive mediator of apoptosis induced by certain cytokines and oncogenes. Here, we identified Gadd45b as an effector of Fas-induced apoptosis and found that p38-mediated Rb hyperphosphorylation is one of the mechanisms of Fas-induced apoptosis in murine hepatocyte AML12 cells. Gadd45b has been shown to activate p38 through its physical interaction with MTK1 and induce apoptosis. However, in this study, we have showed that the function of Gadd45b during Fas-induced apoptosis in AML12 cells is different from that reported in previous studies. Depletion of Gadd45b expression did not inhibit the phosphorylation of p38, but it suppressed p38-mediated Rb phosphorylation and apoptosis in response to Fas stimulation by reducing the interaction between p38 and Rb. Ectopic expression of Gadd45b was sufficient to enhance this interaction. These findings suggest that Gadd45b mediates p38-induced Rb phosphorylation by enhancing the interaction between p38 and Rb during Fas-induced apoptosis in murine hepatocytes.
Gadd45b 被认为是某些细胞因子和癌基因诱导细胞凋亡的正向调节因子。在这里，我们鉴定出 Gadd45b 是 Fas 诱导的凋亡的效应因子，并且发现 Fas 诱导的鼠肝细胞 AML12 细胞凋亡的机制之一是 p38 介导的 Rb 过度磷酸化。已经证明 Gadd45b 通过其与 MTK1 的物理相互作用激活 p38 并诱导细胞凋亡。然而，在这项研究中，我们已经表明 Gadd45b 在 Fas 诱导的 AML12 细胞凋亡中的作用与之前的研究报告不同。Gadd45b 表达的缺失并不抑制 p38 的磷酸化，但通过减少 p38 和 Rb 之间的相互作用，抑制 Fas 刺激下 p38 介导的 Rb 磷酸化和凋亡。Gadd45b 的异位表达足以增强这种相互作用。这些发现表明，Gadd45b 通过增强 Fas 诱导的鼠肝细胞凋亡过程中 p38 和 Rb 之间的相互作用来介导 p38 诱导的 Rb 磷酸化。
