ASB2 is an elongin BC-interacting protein that can assemble with cullin 5 and Rbx1 to reconstitute an E3 ubiquitin ligase complex

The ankyrin repeat-containing protein with a suppressor of cytokine signaling box-2 (ASB2) gene was identified as a retinoic acid-response gene and a target of the promyelocytic leukemia-retinoic acid receptor-a oncogenic protein characteristic of acute promyelocytic leukemia. Expression of AS132 in myeloid leukemia cells inhibits growth and promotes commitment, recapitulating an early step known to be critical for differentiation. Here we show that AS132, by interacting with the Elongin BC complex, can assemble with Cullin5-Rbxl to form an E3 ubiquitin ligase complex that stimulates polyubiquitination by the E2 ubiquitin-conjugating enzyme Ubc5. This is a first indication that a member of the ASB protein family, AS132, is a subunit of an ECS (Elongin C-Cullin-SOCS box)-type E3 ubiquitin ligase complex. Altogether, our results strongly suggest that AS132 targets specific proteins to destruction by the proteasome in leukemia cells that have been induced to differentiate.