Ariadne-2 (ARIH2, Triad1) is a member of the RBR (RING-in-between-RING) family of E3 ligases. It contains a TRIAD motif that harbours 2 RING finger structures. Triad1/ARIH2 catalyses the formation of different poly-ubiquitin chains, which can mark proteins for proteasomal degradation or serve non-proteolytic functions []. It binds the E2 ubiquitin-conjugating enzymes UbcH7 and Ubc13, and this interaction plays a major role in myelopoiesis [, ]. During myeloid differentiation its transcription is activated by HoxA10, a transcription factor []. It is also a regulator of endosomal transport [].Triad1/ARIH2 is involved in regulating the inflammatory response [, ]. ARIH2 physically binds to newly synthesised nuclear hypophosphorylated IkBb and facilitates its ubiquitination and proteasomal degradation. Nuclear hypophosphorylated IkBb, in contrast to the suppressive effects of cytoplasmic IkB, can bind to and activate nuclear p65, promoting NF-kB signaling.
