Letter abstract
Nature Cell Biology 9, 422 - 427 (2007)
Published online: 21 February 2007 | doi:10.1038/ncb1558
Autoregulation of an E2 enzyme by ubiquitin-chain assembly on its catalytic residue
Tommer Ravid1 & Mark Hochstrasser1
Cells have quality-control mechanisms to recognize non-native protein structures and either help the proteins fold or promote their degradation1, 2. 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 proteasome3, 4. 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 reticulum5, 6. 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.
- Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520, USA.
Correspondence to: Mark Hochstrasser1 e-mail: mark.hochstrasser@yale.edu
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