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

Allison Craney, Aileen Kelly, Luying Jia, Indro Fedrigo, Hongtao Yu, Michael Rape

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1540-1545
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
StatePublished - Feb 9 2016


  • APC/C
  • Anaphase-promoting complex
  • Phosphorylation
  • Ube2S
  • Ubiquitin

ASJC Scopus subject areas

  • General


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