ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-binding activity of 4EHP.
The expression of the ubiquitin-like molecule ISG15 and protein modification by ISG15 (ISGylation) are strongly activated by interferon, genotoxic stress, and pathogen infection, suggesting that ISG15 plays an important role in innate immune responses. 4EHP is an mRNA 5' cap structure-binding protein and acts as a translation suppressor by competing with eIF4E for binding to the cap structure. Here, we report that 4EHP is modified by ISG15 and ISGylated 4EHP has a much higher cap structure-binding activity. These data suggest that ISGylation of 4EHP may play an important role in cap structure-dependent translation control in immune responses.
Okumura
Fumihiko
F
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Zou
Weiguo
W
Zhang
Dong-Er
DE
D000595:Amino Acid Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D039561:Eukaryotic Initiation Factor-4E; D006801:Humans; D007113:Immunity, Innate; D008954:Models, Biological; D008969:Molecular Sequence Data; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D039381:RNA Cap-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D012315:RNA Caps / Q000378:metabolism; D014452:Ubiquitins / Q000502:physiology*
D016207:Cytokines; C112609:EIF4E2 protein, human; D039561:Eukaryotic Initiation Factor-4E; D039381:RNA Cap-Binding Proteins; D012315:RNA Caps; D014452:Ubiquitins; C074034:ISG15 protein, human