title: Ube1L and protein ISGylation are not essential for alpha/beta interferon signaling.
abstract: The expression of ubiquitin-like modifier ISG15 and its conjugation to target proteins are highly induced by interferon (IFN) stimulation and during viral and bacterial infections. However, the biological significance of this modification has not been clearly understood. To investigate the function of protein modification by ISG15, we generated a mouse model deficient in UBE1L, an ISG15-activating enzyme. Ube1L-/- mice did not produce ISG15 conjugates but expressed free ISG15 normally. ISGylation has been implicated in the reproduction and innate immunity. However, Ube1L-/- mice were fertile and exhibited normal antiviral responses against vesicular stomatitis virus and lymphocytic choriomeningitis virus infection. Our results indicate that UBE1L and protein ISGylation are not critical for IFN-alpha/beta signaling via JAK/STAT activation. Moreover, using Ube1L/Ubp43 double-deficient mice, we showed that lack of UBP43, but not the increase of protein ISGylation, is related to the increased IFN signaling in Ubp43-deficient mice.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, Mailstop L-51, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Keun Il
authors.initials: KI
authors.lastname: Kim
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Oxana
authors.initials: O
authors.lastname: Malakhova
authors.forename: Jiann-Kae
authors.initials: JK
authors.lastname: Luo
authors.forename: Mei-Feng
authors.initials: MF
authors.lastname: Shen
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zou
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: de la Torre
authors.forename: Dong-Er
authors.initials: DE
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001117:Arenaviridae Infections / Q000276:immunology / Q000378:metabolism / Q000401:mortality; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D043222:Ubiquitin Thiolesterase; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus
chemical_list: D016207:Cytokines; C489550:G1p2 protein, mouse; D016898:Interferon-alpha; D014452:Ubiquitins; D016899:Interferon-beta; D010450:Endopeptidases; C118306:Usp18 protein, mouse; D043222:Ubiquitin Thiolesterase; D044764:Ubiquitin-Activating Enzymes