Negative regulation of protein phosphatase 2Cβ by ISG15 conjugation

Tomoharu Takeuchi, Takayasu Kobayashi, Shinri Tamura, Hideyoshi Yokosawa

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)4521-4526
Number of pages6
JournalFEBS Letters
Issue number18
Publication statusPublished - 2006 Aug 7


  • Interferon
  • Interferon-stimulated gene 15 kDa
  • Nuclear factor κB
  • Protein phosphatase
  • Ubiquitin


Dive into the research topics of 'Negative regulation of protein phosphatase 2Cβ by ISG15 conjugation'. Together they form a unique fingerprint.

Cite this