RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination

TLDR

The study examined multiple RING finger proteins (e.g., BRCA1, Siah‑1, TRC8, NF‑X1, kf‑1, Praja1) for their capacity to mediate E2‑dependent ubiquitination. The authors found that RING finger proteins, including AO7 and the others tested, can be ubiquitinated in an E2‑dependent manner, and that disrupting metal coordination or zinc binding abolishes this activity, indicating a widespread role for RING fingers in protein turnover.

Abstract

A RING finger-containing protein (AO7) that binds ubiquitin-conjugating enzymes (E2s) and is a substrate for E2-dependent ubiquitination was identified. Mutations of cation-coordinating residues within AO7's RING finger abolished ubiquitination, as did chelation of zinc. Several otherwise-unrelated RING finger proteins, including BRCA1, Siah-1, TRC8, NF-X1, kf-1, and Praja1, were assessed for their ability to facilitate E2-dependent ubiquitination. In all cases, ubiquitination was observed. The RING fingers were implicated directly in this activity through mutations of metal-coordinating residues or chelation of zinc. These findings suggest that a large number of RING finger-containing proteins, with otherwise diverse structures and functions, may play previously unappreciated roles in modulating protein levels via ubiquitination.