Negative regulation of protein phosphatase 2Cβ by ISG15 conjugation

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Abstract
ISG15, an interferon-upregulated ubiquitin-like protein, is covalently conjugated to various cellular proteins (ISGylation). In this study, we found that protein phosphatase 2Cβ (PP2Cβ), which functions in the nuclear factor κB (NF-κB) pathway via dephosphorylation of TGF-β-activated kinase, was ISGylated, and analysis by NF-κB luciferase reporter assay revealed that PP2Cβ activity was suppressed by co-expression of ISG15, UBE1L, and UbcH8. We determined the ISGylation sites of PP2Cβ and constructed its ISGylation-resistant mutant. In contrast to the wild type, this mutant suppressed the NF-κB pathway even in the presence of ISG15, UBE1L, and UbcH8. Thus, we propose that ISGylation negatively regulates PP2Cβ activity.http://www.elsevier.com/wps/find/journaldescription.cws_home/506085/descriptio