This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, K. I. Articles by Zhang, D.-E. Search for Related Content PubMed PubMed Citation Articles by Kim, K. I. Articles by Zhang, D.-E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2006, p. 472-479, Vol. 26, No. 2
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.2.472-479.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Ube1L and Protein ISGylation Are Not Essential for Alpha/Beta Interferon Signaling

Keun Il Kim,^1, Ming Yan,¹ Oxana Malakhova,¹ Jiann-Kae Luo,¹ Mei-Feng Shen,¹ Weiguo Zou,¹ Juan Carlos de la Torre,² and Dong-Er Zhang^1*

Department of Molecular and Experimental Medicine,¹ Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037²

Received 16 October 2005/ Accepted 21 October 2005

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-/ß 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.

Present address: Department of Biological Science, Sookmyung Women's University, Seoul 140-742, South Korea.

This article has been cited by other articles:

• Okumura, F., Lenschow, D. J., Zhang, D.-E. (2008). Nitrosylation of ISG15 Prevents the Disulfide Bond-mediated Dimerization of ISG15 and Contributes to Effective ISGylation. J. Biol. Chem. 283: 24484-24488 [Abstract] [Full Text]  
• Kim, M.-J., Hwang, S.-Y., Imaizumi, T., Yoo, J.-Y. (2008). Negative Feedback Regulation of RIG-I-Mediated Antiviral Signaling by Interferon-Induced ISG15 Conjugation. J. Virol. 82: 1474-1483 [Abstract] [Full Text]  
• Martin, S. A. M., Taggart, J. B., Seear, P., Bron, J. E., Talbot, R., Teale, A. J., Sweeney, G. E., Hoyheim, B., Houlihan, D. F., Tocher, D. R., Zou, J., Secombes, C. J. (2007). Interferon type I and type II responses in an Atlantic salmon (Salmo salar) SHK-1 cell line by the salmon TRAITS/SGP microarray. Physiol. Genomics 32: 33-44 [Abstract] [Full Text]  
• Yan, M., Luo, J.-K., Ritchie, K. J., Sakai, I., Takeuchi, K., Ren, R., Zhang, D.-E. (2007). Ubp43 regulates BCR-ABL leukemogenesis via the type 1 interferon receptor signaling. Blood 110: 305-312 [Abstract] [Full Text]  
• Okumura, F., Zou, W., Zhang, D.-E. (2007). ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-binding activity of 4EHP. Genes Dev. 21: 255-260 [Abstract] [Full Text]  
• Zou, W., Zhang, D.-E. (2006). The Interferon-inducible Ubiquitin-protein Isopeptide Ligase (E3) EFP Also Functions as an ISG15 E3 Ligase. J. Biol. Chem. 281: 3989-3994 [Abstract] [Full Text]