Xu Ye, Yang Guohua, Hu Gengxi
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Acta Biochim Biophys Sin (Shanghai). 2009 Jun;41(6):488-94. doi: 10.1093/abbs/gmp034.
Interferon-induced transmembrane protein 1 (IFITM1) is an essential mediator of interferon-g-induced antiproliferation. Here, we reported the interaction between IFITM1 and caveolin-1 (CAV-1), and their inhibitory regulatory function on extracellular signal-regulated kinase (ERK). The immunofluorescence staining result showed that IFITM1 localized in caveolae of the plasma membrane and could interact with CAV-1. Deletion mutagenesis clearly revealed that the hydrophobic transmembrane domains were responsible for the interaction between IFITM1 and CAV-1. It has been reported that CAV-1 has inhibitory effect on the phosphorylation of ERK, and subsequently ERK-mediated transcription. Our study showed the interaction of IFITM1- and CAV-1-enhanced CAV-1's inhibitory effect on ERK activation, whereas the IFITM1 did not activate ERK directly. This inhibitory effect was further confirmed by knocking down the endogenous CAV-1 using RNA interference. These results revealed that the interaction between IFITM1 and CAV-1 could enhance the inhibitory effect of CAV-1 on ERK activation.
干扰素诱导跨膜蛋白1（IFITM1）是干扰素γ诱导的抗增殖作用的重要介质。在此，我们报道了IFITM1与小窝蛋白1（CAV-1）之间的相互作用，以及它们对细胞外信号调节激酶（ERK）的抑制调节功能。免疫荧光染色结果显示，IFITM1定位于质膜的小窝中，并可与CAV-1相互作用。缺失突变分析清楚地表明，疏水跨膜结构域是IFITM1与CAV-1之间相互作用的原因。据报道，CAV-1对ERK的磷酸化以及随后ERK介导的转录具有抑制作用。我们的研究表明，IFITM1与CAV-1的相互作用增强了CAV-1对ERK激活的抑制作用，而IFITM1本身并不直接激活ERK。使用RNA干扰敲低内源性CAV-1进一步证实了这种抑制作用。这些结果表明，IFITM1与CAV-1之间的相互作用可增强CAV-1对ERK激活的抑制作用。
