RIOK3 interacts with caspase-10 and negatively regulates the NF-κB signaling pathway

Jingxuan Shan, Pingzhang Wang, Juan Zhou, Donghua Wu, Huili Shi, Keke Huo

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

RIOK3 was initially characterized as a homolog of Aspergillus nidulans sudD and showed down-regulation at the invasive front of malignant melanomas, but the molecular mechanism remains elusive. Here, we report that overexpression of RIOK3 inhibits TNFα-induced NF-κB activation, but down-regulation of endogenous RIOK3 expression by siRNA potentiates it. A yeast two-hybrid experiment revealed that RIOK3 interacted with caspase-10, and further, a GST pull-down assay and endogenous coimmunoprecipitation validated the interaction. We subsequently showed that the interaction was mediated by the RIO domain of RIOK3 and each death effector domain of caspase-10. Interestingly, our data demonstrated that RIOK3 suppressed caspase-10-mediated NF-κB activation by competing RIP1 and NIK to bind to caspase-10. Importantly, the kinase activity of RIOK3 was confirmed to be relevant to NF-κB signaling. Taken together, our findings strongly suggest that RIOK3 negatively regulates NF-κB signaling pathway activated by TNFα dependent on its kinase activity and NF-κB signaling pathway activated by caspase-10 independent of its kinase activity.

Original languageEnglish
Pages (from-to)113-120
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume332
Issue number1-2
DOIs
Publication statusPublished - 1 Jan 2009

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Keywords

  • Caspase-10
  • NF-κB activation
  • RIOK3
  • TNFα

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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