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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,{dagger} 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 Zhang1*

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-{alpha}/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.

* Corresponding author. Mailing address: Department of Molecular and Experimental Medicine, The Scripps Research Institute, Mailstop L-51, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: (858) 784-9558. Fax: (858) 784-9593. E-mail: dzhang{at}scripps.edu.

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

Molecular and Cellular Biology, January 2006, p. 472-479, Vol. 26, No. 2
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.2.472-479.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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