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Proc Natl Acad Sci U S A. 2016 Feb 9;113(6):1540-5. doi: 10.1073/pnas.1522423113. Epub 2016 Jan 25.

Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation.

Author information

1
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
2
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390;
3
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720 mrape@berkeley.edu.

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 PP2A(B56) allows Ube2S to bind the APC/C and catalyze ubiquitin chain elongation. PP2A(B56) 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; Ube2S; anaphase-promoting complex; phosphorylation; ubiquitin

PMID:
26811472
PMCID:
PMC4760819
DOI:
10.1073/pnas.1522423113
[Indexed for MEDLINE]
Free PMC Article

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