Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 332, Issue 1-2, Pages 113-120Publisher
SPRINGER
DOI: 10.1007/s11010-009-0180-8
Keywords
RIOK3; NF-kappa B activation; TNF alpha; Caspase-10
Categories
Funding
- Chinese 863 program [2006AA02A310]
- Chinese Human Liver Proteome Project [2004BA711A19]
Ask authors/readers for more resources
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 TNF alpha-induced NF-kappa B 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-kappa B activation by competing RIP1 and NIK to bind to caspase-10. Importantly, the kinase activity of RIOK3 was confirmed to be relevant to NF-kappa B signaling. Taken together, our findings strongly suggest that RIOK3 negatively regulates NF-kappa B signaling pathway activated by TNF alpha dependent on its kinase activity and NF-kappa B signaling pathway activated by caspase-10 independent of its kinase activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available