E3 ISG15--protein ligase HERC5

Definition:

Major E3 ligase for ISG15 conjugation. Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant-negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15.

References:

[1]. YuJie Tang, et al. Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein. J Immunol. 2010 May 15;184(10):5777-90. [Content Brief]

[2]. Tomoharu Takeuchi, et al. Identification and Herc5-mediated ISGylation of novel target proteins. Biochem Biophys Res Commun. 2006 Sep 22;348(2):473-7. [Content Brief]

[3]. He-Xin Shi, et al. Positive regulation of interferon regulatory factor 3 activation by Herc5 via ISG15 modification. Mol Cell Biol. 2010 May;30(10):2424-36. [Content Brief]

[4]. Anahita Dastur, et al. Herc5, an interferon-induced HECT E3 enzyme, is required for conjugation of ISG15 in human cells. J Biol Chem. 2006 Feb 17;281(7):4334-8. [Content Brief]

[5]. Chen Zhao, et al. ISG15 conjugation system targets the viral NS1 protein in influenza A virus-infected cells. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2253-8. [Content Brief]

[6]. Larissa A Durfee, et al. The ISG15 conjugation system broadly targets newly synthesized proteins: implications for the antiviral function of ISG15. Mol Cell. 2010 Jun 11;38(5):722-32. [Content Brief]

[7]. Joyce Jing Yi Wong, et al. HERC5 is an IFN-induced HECT-type E3 protein ligase that mediates type I IFN-induced ISGylation of protein targets. Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10735-40. [Content Brief]

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