Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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 TNFalpha-induced NF-kappaB 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-kappaB activation by competing RIP1 and NIK to bind to caspase-10. Importantly, the kinase activity of
RIOK3
was confirmed to be relevant to NF-kappaB signaling. Taken together, our findings strongly suggest that
RIOK3
negatively regulates NF-kappaB signaling pathway activated by TNFalpha dependent on its kinase activity and NF-kappaB signaling pathway activated by caspase-10 independent of its kinase activity.
...
PMID:RIOK3 interacts with caspase-10 and negatively regulates the NF-kappaB signaling pathway. 1955 2
