RNF125 acts as an E3-ubiquitin ligase that conjugates with RIG-I, MDA5 and IPS-1 and mediate their proteosomal degradation. UbcH1, UbcH5a, UbcH5b, and UbcH5c function as an E2 enzyme and conjugate ubiquitin to RNF125 and RIG-1 via K48. Among these enzymes UbcH5c is the major E2 enzyme showing enhanced ubiquitin conjugation to RIG-I. RNF125 mediated ubiquitination of RIG-I/MDA5 and IPS1 inhibits RIG-I signaling by shunting these proteins toward proteasomal degradation.
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