Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.10 (IKK)
 4,900 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RNA helicase retinoic inducible gene I (RIG-I) recognizes viral double-stranded RNA and initiates signaling cascades that lead to activation of the protein kinases IKKalphabeta, TBK1 and IKKepsilon, and to subsequent activation of the transcription factors NF-kappaB and IRF3. We recently reported that RIG-I was ubiquitinated by RNF125, an ubiquitin E3 ligase, leading to proteasomal degradation. RIG-I is also reported to be ISGylated by an unidentified ISG15 (IFN-stimulated gene, 15kDa) E3 ligase. UbcH8, an ubiquitin E2 conjugating enzyme, was shown to be involved in RIG-I ISGylation. Here, we found that UbcH8 suppressed RIG-I ubiquitination by RNF125, and this suppression was relieved by ectopic expression of ISG15. Alternately, ISG15 conjugation to RIG-I was suppressed by RNF125. By analyzing this regulatory circuit, we found that UbcH8 and ISG15 are functional regulators of RNF125 E3 ligase activity, which regulates the level of ubiquitin and ISG15 conjugation of RIG-I.
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PMID:UbcH8 regulates ubiquitin and ISG15 conjugation to RIG-I. 1771 35