@article{5a108336d5904ac6ae93833fa9523e4c,
title = "Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation",
abstract = "Most metazoan E3 ligases contain a signature RING domain that promotes the transfer of ubiquitin from the active site of E2 conjugating enzymes to lysine residues in substrates. Although these RING-E3s depend on E2 enzymes for catalysis, how they turn on their E2s at the right time and place remains poorly understood. Here we report a phosphorylation-dependent mechanism that ensures timely activation of the E2 Ube2S by its RING-E3, the anaphase- promoting complex (APC/C); while phosphorylation of a specific serine residue in the APC/C coactivator Cdc20 prevents delivery of Ube2S to the APC/C, removal of this mark by PP2AB56 allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2AB56 also stabilizes kinetochore-microtubule attachments to shut off the spindle checkpoint, suggesting that cells regulate the E2-E3 interplay to coordinate ubiquitination with critical events during cell division.",
keywords = "APC/C, Anaphase-promoting complex, Phosphorylation, Ube2S, Ubiquitin",
author = "Allison Craney and Aileen Kelly and Luying Jia and Indro Fedrigo and Hongtao Yu and Michael Rape",
note = "Funding Information: We thank Vishva Dixit and Marissa Matsumoto (Genentech) for the gift of αK11-antibodies, and Rebecca Heald for the gift of mCherry-histone H2B/GFP-tubulin HeLa cells. We also thank Julia Schaletzky, Rebecca Heald, Iain Cheeseman, Julie Welburn, and members of the M.R. laboratory for advice and stimulating discussions. This work was performed using the Vincent J. Coates Proteomics/Mass Spectrometry Laboratory at University of California, Berkeley (supported by National Institutes of Health Grants S10RR029668, S10RR027303, and S10RR025622). A.C. was funded in part by a fellowship from the National Science Foundation. This work was funded by a grant from the National Institutes of Health (to M.R.). M.R. is the K. Peter Hirth Chair of Cancer Biology at University of California, Berkeley. H.Y. and M.R. are investigators with the Howard Hughes Medical Institute. Funding Information: We thank Vishva Dixit and Marissa Matsumoto (Genentech) for the gift of ?K11-antibodies, and Rebecca Heald for the gift of mCherry-histone H2B/GFP-tubulin HeLa cells. We also thank Julia Schaletzky, Rebecca Heald, Iain Cheeseman, Julie Welburn, and members of the M.R. laboratory for advice and stimulating discussions. This work was performed using the Vincent J. Coates Proteomics/Mass Spectrometry Laboratory at University of California, Berkeley (supported by National Institutes of Health Grants S10RR029668, S10RR027303, and S10RR025622). A.C. was funded in part by a fellowship from the National Science Foundation. This work was funded by a grant from the National Institutes of Health (to M.R.). M.R. is the K. Peter Hirth Chair of Cancer Biology at University of California, Berkeley. H.Y. and M.R. are investigators with the Howard Hughes Medical Institute.",
year = "2016",
month = feb,
day = "9",
doi = "10.1073/pnas.1522423113",
language = "English (US)",
volume = "113",
pages = "1540--1545",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "6",
}