RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination.
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.
Lorick
K L
KL
Laboratory of Immune Cell Biology, Division of Basic Sciences, National Cancer Institute, Building 10, Room 1B34, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-1152, USA.
Jensen
J P
JP
Fang
S
S
Ong
A M
AM
Hatakeyama
S
S
Weissman
A M
AM
D000595:Amino Acid Sequence; D008025:Ligases / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D044763:Ubiquitin-Conjugating Enzymes; D014452:Ubiquitins / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology; D016335:Zinc Fingers
D014452:Ubiquitins; C097309:UBE2D2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases; D015032:Zinc