title: Binding of IFITM1 enhances the inhibiting effect of caveolin-1 on ERK activation.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.forename: Guohua
authors.initials: G
authors.lastname: Yang
authors.forename: Gengxi
authors.initials: G
authors.lastname: Hu
mesh_terms: D000943:Antigens, Differentiation; D001483:Base Sequence; D051242:Caveolin 1 / Q000494:pharmacology*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering
chemical_list: D000943:Antigens, Differentiation; D051242:Caveolin 1; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C062010:leu-13 antigen; D048049:Extracellular Signal-Regulated MAP Kinases