UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex.
The Anaphase-Promoting Complex (APC) is an E3 ubiquitin ligase that regulates mitosis and G1 by sequentially targeting cell-cycle regulators for ubiquitination and proteasomal degradation. The mechanism of ubiquitin chain formation by APC and the resultant chain topology remains controversial. By using a single-lysine APC substrate to dissect the topology of ... ubiquitinated substrates, we find that APC-catalyzed ubiquitination has an intrinsic preference for the K11 linkage of ubiquitin that is essential for substrate degradation. K11 specificity is determined by an E2 enzyme, UBE2S/E2-EPF, that elongates ubiquitin chains after the substrates are pre-ubiquitinated by UbcH10 or UbcH5. UBE2S copurifies with APC; dominant-negative Ube2S slows down APC substrate degradation in functional cell-cycle extracts. We propose that Ube2S is a critical, unique component of the APC ubiquitination pathway.
Mesh Terms:
Biocatalysis, Cell Cycle, Hela Cells, Humans, Lysine, Mutation, Neoplasm Proteins, Protein Binding, Substrate Specificity, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes
Biocatalysis, Cell Cycle, Hela Cells, Humans, Lysine, Mutation, Neoplasm Proteins, Protein Binding, Substrate Specificity, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes
Proc. Natl. Acad. Sci. U.S.A.
Date: Jan. 26, 2010
PubMed ID: 20080579
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