The BioGRID | PUBLICATION VIEW

	Nat. Cell Biol. Apr (2007); 9(4):422-7
Autoregulation of an E2 enzyme by ubiquitin-chain assembly on its catalytic residue-
Ravid T, Hochstrasser M
Department of Molecular Biophysics - Biochemistry, Yale University, New Haven, CT 06520, USA-
Abstract: Cells have quality-control mechanisms to recognize non-native protein structures and either help the proteins fold or promote their degradation- Ubiquitin-conjugating enzymes -E2s- and ubiquitin ligases -E3s- work together to assemble polyubiquitin chains on misfolded or misassembled proteins, which are then degraded by the proteasome- Here, we find that Ubc7, a yeast E2, can itself undergo degradation when its levels exceed that of its binding partner Cue1, a transmembrane protein that tethers Ubc7 to the endoplasmic reticulum- Unassembled, and thus mislocalized, Ubc7 is targeted to the proteasome by Ufd4, a homologous to E6-AP C-terminus -HECT--class E3- Ubc7 is autoubiquitinated by a novel mechanism wherein the catalytic cysteine, instead of a lysine residue, provides the polyubiquitin chain acceptor site, and this cysteine-linked chain functions as a degradation signal- The polyubiquitin chain can also be transferred to a lysine side chain, suggesting a mechanism for polyubiquitin chain assembly that precedes substrate modification-
[PUBMED: 17310239]