Identification and Validation of ISG15 Target Proteins - PubMed (original) (raw)

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Identification and Validation of ISG15 Target Proteins

Larissa A Durfee et al. Subcell Biochem. 2010.

Abstract

ISG15 is an interferon-induced ubiquitin-like protein (Ubl) that has antiviral properties. The core E1, E2 and E3 enzymes for conjugation of human ISG15 are Ube1L, UbcH8 and Herc5, all of which are induced at the transcriptional level by Type 1 interferon signaling. Several proteomics studies have, together, identified over 300 cellular proteins as ISG15 targets. These targets include a broad range of constitutively expressed proteins and approximately 15 interferon-induced proteins. This chapter provides an overview of the target identification process and the validation of these targets. We also discuss the limited number of examples where the biochemical effect of ISG15 conjugation on target proteins has been characterized.

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Figures

Figure 1

Important discoveries in the ISG15 field. The timeline highlights the progress made since the discovery of ISG15 in 1979.

Figure 2

Timecourse of total ISG15 conjugation in non-interferon-treated cells. HEK293T cells were transfected with plasmids expressing Ube1L, UbcH8, Herc5 and 3X-FLAG-ISG15. Cell extracts were collected at the indicated time points and analyzed by immunoblotting with anti-FLAG antibody.

Figure 3

ISG15 conjugation to exogenously expressed targets is enhanced by the co-expression of Herc5. HEK293T cells were transfected with a plasmid expressing an epitope-tagged target protein either alone (lane 1), or combined with Ube1L, UbcH8 and ISG15 (lane 2), or combined with Ube1L, UbcH8, ISG15 and Herc5 (lane 3). Cell extracts were prepared 48 hours posttransfection and analyzed by immunoblotting using the indicated antibodies.

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Identification and Validation of ISG15 Target Proteins - PubMed (original) (raw)