Fbs2 Is a New Member of the E3 Ubiquitin Ligase Family That Recognizes Sugar Chains
F-box proteins are substrate recognition components of Skp1-Cullin1-F-box protein-Roc1 (SCF) E3 ubiquitin-protein ligases. We reported previously that Fbs1 (F-box protein that recognizes sugar chains; equivalent to Fbx2 or NFB42) binds specifically to proteins attached with high mannose oligosaccharides and subsequently contributes to elimination of N-glycoproteins in cytosol (Yoshida, Y., Chiba, T., Tokunaga, F., Kawasaki, H., Iwai, K., Suzuki, T., Ito, Y., Matsuoka, K., Yoshida, M., Tanaka, K., and Tai, T. (2002) Nature 418, 438–442). Here we report the identification of another F-box protein that recognizes N-glycan, Fbs2 (called Fbx6b or FBG2 previously). Although the expression of Fbs1 was restricted to the adult brain and testis, the Fbs2 transcript was widely expressed. The Fbs2 protein forms an SCFFbs2 ubiquitinligase complex that targets sugar chains in N-glycoproteins for ubiquitylation. Only glycoproteins bound to concanavalin A lectin and not to wheat germ agglutinin or Ricinus communis agglutinin interacted with Fbs2 in various tissues and cell lines. Pull-down analysis using various oligosaccharides revealed that Man3–9GlcNAc2 glycans for Fbs2 of mannose or of Fbs2 Fbs2 interacted with of substrate of the and the expression of the F-box for the and of Fbs2 to of in Fbs2 of F-box protein that recognizes and in F-box proteins are substrate recognition components of Skp1-Cullin1-F-box protein-Roc1 (SCF) E3 ubiquitin-protein ligases. We reported previously that Fbs1 (F-box protein that recognizes sugar chains; equivalent to Fbx2 or NFB42) binds specifically to proteins attached with high mannose oligosaccharides and subsequently contributes to elimination of N-glycoproteins in cytosol (Yoshida, Y., Chiba, T., Tokunaga, F., Kawasaki, H., Iwai, K., Suzuki, T., Ito, Y., Matsuoka, K., Yoshida, M., Tanaka, K., and Tai, T. (2002) Nature 418, 438–442). Here we report the identification of another F-box protein that recognizes N-glycan, Fbs2 (called Fbx6b or FBG2 previously). Although the expression of Fbs1 was restricted to the adult brain and testis, the Fbs2 transcript was widely expressed. The Fbs2 protein forms an SCFFbs2 ubiquitinligase complex that targets sugar chains in N-glycoproteins for ubiquitylation. Only glycoproteins bound to concanavalin A lectin and not to wheat germ agglutinin or Ricinus communis agglutinin interacted with Fbs2 in various tissues and cell lines. Pull-down analysis using various oligosaccharides revealed that Man3–9GlcNAc2 glycans for Fbs2 of mannose or of Fbs2 Fbs2 interacted with of substrate of the and the expression of the F-box for the and of Fbs2 to of in Fbs2 of F-box protein that recognizes and in protein the in of the of or protein the ubiquitin-protein concanavalin wheat germ Ricinus Skp1-Cullin1-F-box ubiquitin-protein concanavalin wheat germ Ricinus Skp1-Cullin1-F-box the and the ubiquitin-protein the E3 an in the of proteins for E3 binds protein substrate with of for ubiquitylation. are to with in of are of the E3 the Skp1-Cullin1-F-box protein-Roc1 (SCF) complex The of and of of proteins F-box F-box proteins with an of and that with the substrate the of the F-box protein to proteins that of proteins for recognition that of the for the the we reported that Fbx2 forms an complex that targets sugar chains in glycoproteins for T. T. T. 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