Gene interactions and pathways from curated databases and text-mining
Cell 2008, PMID: 18485873

Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex.

Jin, Lingyan; Williamson, Adam; Banerjee, Sudeep; Philipp, Isabelle; Rape, Michael

The anaphase-promoting complex (APC/C) orchestrates progression through mitosis by decorating cell-cycle regulators with ubiquitin chains. To nucleate chains, the APC/C links ubiquitin to a lysine in substrates, but to elongate chains it modifies lysine residues in attached ubiquitin moieties. The mechanism enabling the APC/C, and ubiquitin ligases in general, to switch from lysine residues in substrates to specific ones in ubiquitin remains poorly understood. Here, we determine the topology and the mechanism of assembly for the ubiquitin chains mediating functions of the human APC/C. We find that the APC/C triggers substrate degradation by assembling K11-linked ubiquitin chains, the efficient formation of which depends on a surface of ubiquitin, the TEK-box. Strikingly, homologous TEK-boxes are found in APC/C substrates, where they facilitate chain nucleation. We propose that recognition of similar motifs in substrates and ubiquitin enables the APC/C to assemble ubiquitin chains with the specificity and efficiency required for tight cell-cycle control.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: CCNA2 — FZR1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: FZR1 — UBE2D1 (direct interaction, pull down)
  • IRef Biogrid Interaction: FZR1 — UBE2K (direct interaction, pull down)
  • IRef Biogrid Interaction: FZR1 — UBE2C (direct interaction, pull down)
  • IRef Biogrid Interaction: CCNA2 — PSMD4 (direct interaction, pull down)
  • IRef Biogrid Interaction: FZR1 — UBE2D3 (direct interaction, pull down)
  • IRef Biogrid Interaction: FZR1 — PTTG1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: CCNA2 — RAD23A (direct interaction, pull down)
  • IRef Biogrid Interaction: PTTG1 — RAD23A (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PTTG1 — UBC (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: UBE2C — UBE2C (direct interaction, enzymatic study)
  • Gene Ontology Complexes anaphase-promoting complex: anaphase-promoting complex complex (MAD2L2-ANAPC2-CDC23-ANAPC15-CDC26-UBE2C-ANAPC16-ANAPC11-ANAPC13-CDC20-FZR1-ANAPC1-CUL7-ANAPC4-ANAPC7)
  • Reactome Reaction: UBA52 → ANAPC1 (reaction)
  • Reactome Reaction: ANAPC4 → CDC26 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC2 (reaction)
  • Reactome Reaction: ANAPC5 → UBC (reaction)
  • Reactome Reaction: UBE2D1 → UBE2C (reaction)
  • Reactome Reaction: PTTG1 → UBE2C (indirect_complex)
  • Reactome Reaction: ANAPC5 → UBB (reaction)
  • Reactome Reaction: ANAPC4 → ANAPC4 (reaction)
  • Reactome Reaction: ANAPC5 → CDC26 (reaction)
  • Reactome Reaction: ANAPC1 → ANAPC1 (reaction)
  • Reactome Reaction: UBE2D1 → CDC26 (reaction)
  • Reactome Reaction: ANAPC10 → ANAPC10 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC1 (indirect_complex)
  • Reactome Reaction: ANAPC4 → ANAPC10 (reaction)
  • Reactome Reaction: UBE2E1 → ANAPC10 (reaction)
  • Reactome Reaction: ANAPC11 → ANAPC4 (reaction)
  • Reactome Reaction: UBE2E1 → ANAPC7 (reaction)
  • Reactome Reaction: ANAPC4 → CDC16 (reaction)
  • Reactome Reaction: ANAPC2 → CDC20 (reaction)
  • Reactome Reaction: UBE2E1 → ANAPC11 (reaction)
  • Reactome Reaction: PTTG1 → UBA52 (reaction)
  • Reactome Reaction: ANAPC5 → CDC20 (reaction)
  • Reactome Reaction: UBA52 → CDC16 (reaction)
  • Reactome Reaction: ANAPC7 → CDC23 (reaction)
  • Reactome Reaction: ANAPC11 → ANAPC10 (reaction)
  • Reactome Reaction: RPS27A → ANAPC4 (reaction)
  • Reactome Reaction: ANAPC11 → CDC27 (reaction)
  • Reactome Reaction: ANAPC2 → CDC23 (reaction)
  • Reactome Reaction: UBE2D1 → ANAPC1 (reaction)
  • Reactome Reaction: UBE2D1 → UBE2E1 (reaction)
  • Reactome Reaction: CDC23 → UBB (reaction)
  • Reactome Reaction: UBE2C → ANAPC4 (reaction)
  • Reactome Reaction: ANAPC11 → UBB (reaction)
  • Reactome Reaction: UBE2C → CDC23 (reaction)
  • Reactome Reaction: PTTG1 → UBC (reaction)
  • Reactome Reaction: ANAPC11 → CDC20 (reaction)
  • Reactome Reaction: UBA52 → ANAPC5 (reaction)
  • Reactome Reaction: CDC27 → CDC27 (reaction)
  • Reactome Reaction: ANAPC11 → ANAPC7 (reaction)
  • Reactome Reaction: ANAPC11 → UBA52 (reaction)
  • Reactome Reaction: UBE2E1 → UBE2C (reaction)
  • Reactome Reaction: UBE2C → UBB (reaction)
  • Reactome Reaction: CDC16 → UBB (reaction)
  • Reactome Reaction: UBE2C → CDC20 (reaction)
  • Reactome Reaction: CDC27 → CDC26 (reaction)
  • Reactome Reaction: ANAPC10 → CDC16 (reaction)
  • Reactome Reaction: ANAPC1 → ANAPC10 (reaction)
  • Reactome Reaction: UBE2C → RPS27A (reaction)
  • Reactome Reaction: ANAPC1 → ANAPC7 (reaction)
  • Reactome Reaction: RPS27A → ANAPC1 (reaction)
  • Reactome Reaction: PTTG1 → UBE2C (reaction)
  • Reactome Reaction: UBE2D1 → UBA52 (reaction)
  • Reactome Reaction: ANAPC10 → CDC20 (reaction)
  • Reactome Reaction: ANAPC1 → UBB (reaction)
  • Reactome Reaction: UBE2C → ANAPC7 (reaction)
  • Reactome Reaction: UBA52 → CDC26 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC5 (reaction)
  • Reactome Reaction: CDC27 → UBE2C (reaction)
  • Reactome Reaction: UBE2D1 → CDC23 (reaction)
  • Reactome Reaction: ANAPC7 → CDC20 (reaction)
  • Reactome Reaction: ANAPC1 → ANAPC5 (reaction)
  • Reactome Reaction: UBE2E1 → RPS27A (reaction)
  • Reactome Reaction: ANAPC7 → UBB (reaction)
  • Reactome Reaction: ANAPC7 → CDC16 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC4 (reaction)
  • Reactome Reaction: ANAPC5 → ANAPC7 (reaction)
  • Reactome Reaction: UBA52 → ANAPC7 (reaction)
  • Reactome Reaction: CDC27 → CDC23 (reaction)
  • Reactome Reaction: CDC27 → UBA52 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC7 (indirect_complex)
  • Reactome Reaction: CDC16 → CDC20 (reaction)
  • Reactome Reaction: CDC27 → CDC20 (reaction)
  • Reactome Reaction: RPS27A → CDC26 (reaction)
  • Reactome Reaction: UBE2E1 → ANAPC5 (reaction)
  • Reactome Reaction: UBA52 → ANAPC4 (reaction)
  • Reactome Reaction: ANAPC1 → CDC26 (reaction)
  • Reactome Reaction: ANAPC5 → ANAPC5 (reaction)
  • Reactome Reaction: ANAPC2 → ANAPC10 (reaction)
  • Reactome Reaction: PTTG1 → UBE2D1 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC5 (indirect_complex)
  • Reactome Reaction: ANAPC7 → UBC (reaction)
  • Reactome Reaction: RPS27A → ANAPC7 (reaction)
  • Reactome Reaction: CDC20 → UBC (reaction)
  • Reactome Reaction: CDC20 → UBB (reaction)
  • Reactome Reaction: ANAPC2 → ANAPC2 (reaction)
  • Reactome Reaction: CDC16 → CDC26 (reaction)
  • Reactome Reaction: CDC26 → CDC26 (reaction)
  • Reactome Reaction: UBE2D1 → ANAPC10 (reaction)
  • Reactome Reaction: CDC27 → ANAPC1 (reaction)
  • Reactome Reaction: ANAPC11 → ANAPC11 (reaction)
  • Reactome Reaction: ANAPC7 → ANAPC10 (reaction)
  • Reactome Reaction: UBE2C → CDC16 (reaction)
  • Reactome Reaction: ANAPC4 → UBC (reaction)
  • Reactome Reaction: RPS27A → CDC23 (reaction)
  • Reactome Reaction: ANAPC2 → UBC (reaction)
  • Reactome Reaction: UBE2C → UBE2C (reaction)
  • Reactome Reaction: UBE2D1 → CDC20 (reaction)
  • Reactome Reaction: UBE2E1 → UBC (reaction)
  • Reactome Reaction: ANAPC1 → ANAPC2 (reaction)
  • Reactome Reaction: ANAPC11 → ANAPC1 (reaction)
  • Reactome Reaction: UBE2E1 → ANAPC1 (reaction)
  • Reactome Reaction: UBE2C → ANAPC10 (reaction)
  • Reactome Reaction: UBE2D1 → CDC27 (reaction)
  • Reactome Reaction: ANAPC4 → ANAPC7 (reaction)
  • Reactome Reaction: RPS27A → ANAPC10 (reaction)
  • Reactome Reaction: UBE2E1 → UBB (reaction)
  • Reactome Reaction: UBE2E1 → ANAPC2 (reaction)
  • Reactome Reaction: UBE2E1 → UBA52 (reaction)
  • Reactome Reaction: PTTG1 → CDC20 (reaction)
  • Reactome Reaction: ANAPC11 → UBE2C (reaction)
  • Reactome Reaction: CDC16 → UBC (reaction)
  • Reactome Reaction: ANAPC2 → ANAPC4 (reaction)
  • Reactome Reaction: UBE2D1 → CDC16 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC10 (indirect_complex)
  • Reactome Reaction: UBE2C → UBC (reaction)
  • Reactome Reaction: ANAPC5 → ANAPC10 (reaction)
  • Reactome Reaction: UBE2D1 → ANAPC5 (reaction)
  • Reactome Reaction: ANAPC1 → CDC20 (reaction)
  • Reactome Reaction: CDC23 → CDC23 (reaction)
  • Reactome Reaction: UBE2C → CDC26 (reaction)
  • Reactome Reaction: UBE2C → UBA52 (reaction)
  • Reactome Reaction: PTTG1 → UBE2E1 (indirect_complex)
  • Reactome Reaction: ANAPC5 → CDC16 (reaction)
  • Reactome Reaction: PTTG1 → UBB (reaction)
  • Reactome Reaction: UBE2D1 → ANAPC11 (reaction)
  • Reactome Reaction: ANAPC1 → CDC16 (reaction)
  • Reactome Reaction: UBE2D1 → ANAPC4 (reaction)
  • Reactome Reaction: PTTG1 → CDC20 (indirect_complex)
  • Reactome Reaction: ANAPC1 → CDC23 (reaction)
  • Reactome Reaction: UBE2C → ANAPC5 (reaction)
  • Reactome Reaction: CDC27 → ANAPC5 (reaction)
  • Reactome Reaction: ANAPC10 → CDC26 (reaction)
  • Reactome Reaction: CDC23 → UBC (reaction)
  • Reactome Reaction: RPS27A → CDC20 (reaction)
  • Reactome Reaction: UBE2D1 → ANAPC7 (reaction)
  • Reactome Reaction: ANAPC10 → UBB (reaction)
  • Reactome Reaction: UBE2D1 → RPS27A (reaction)
  • Reactome Reaction: PTTG1 → ANAPC1 (reaction)
  • Reactome Reaction: UBA52 → CDC20 (reaction)
  • Reactome Reaction: CDC27 → ANAPC4 (reaction)
  • Reactome Reaction: UBE2D1 → UBB (reaction)
  • Reactome Reaction: RPS27A → ANAPC2 (reaction)
  • Reactome Reaction: ANAPC11 → CDC23 (reaction)
  • Reactome Reaction: PTTG1 → CDC16 (reaction)
  • Reactome Reaction: PTTG1 → CDC23 (reaction)
  • Reactome Reaction: CDC20 → CDC23 (reaction)
  • Reactome Reaction: PTTG1 → CDC27 (indirect_complex)
  • Reactome Reaction: UBE2E1 → CDC26 (reaction)
  • Reactome Reaction: UBE2D1 → UBC (reaction)
  • Reactome Reaction: ANAPC1 → ANAPC4 (reaction)
  • Reactome Reaction: CDC27 → CDC16 (reaction)
  • Reactome Reaction: ANAPC4 → CDC23 (reaction)
  • Reactome Reaction: UBA52 → ANAPC2 (reaction)
  • Reactome Reaction: UBA52 → CDC23 (reaction)
  • Reactome Reaction: UBE2E1 → CDC27 (reaction)
  • Reactome Reaction: CDC27 → UBB (reaction)
  • Reactome Reaction: UBE2E1 → UBE2E1 (reaction)
  • Reactome Reaction: CDC16 → CDC16 (reaction)
  • Reactome Reaction: PTTG1 → CDC26 (indirect_complex)
  • Reactome Reaction: PTTG1 → UBE2D1 (indirect_complex)
  • Reactome Reaction: CDC27 → UBC (reaction)
  • Reactome Reaction: ANAPC10 → UBC (reaction)
  • Reactome Reaction: ANAPC2 → UBB (reaction)
  • Reactome Reaction: ANAPC2 → CDC16 (reaction)
  • Reactome Reaction: ANAPC10 → CDC23 (reaction)
  • Reactome Reaction: UBE2D1 → UBE2D1 (reaction)
  • Reactome Reaction: UBA52 → ANAPC10 (reaction)
  • Reactome Reaction: PTTG1 → CDC27 (reaction)
  • Reactome Reaction: UBE2C → ANAPC2 (reaction)
  • Reactome Reaction: UBE2E1 → CDC16 (reaction)
  • Reactome Reaction: ANAPC5 → CDC23 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC11 (indirect_complex)
  • Reactome Reaction: RPS27A → CDC16 (reaction)
  • Reactome Reaction: ANAPC11 → CDC16 (reaction)
  • Reactome Reaction: ANAPC11 → RPS27A (reaction)
  • Reactome Reaction: ANAPC4 → CDC20 (reaction)
  • Reactome Reaction: UBE2E1 → CDC23 (reaction)
  • Reactome Reaction: UBE2D1 → ANAPC2 (reaction)
  • Reactome Reaction: ANAPC11 → CDC26 (reaction)
  • Reactome Reaction: ANAPC4 → UBB (reaction)
  • Reactome Reaction: RPS27A → ANAPC5 (reaction)
  • Reactome Reaction: UBE2C → ANAPC1 (reaction)
  • Reactome Reaction: CDC27 → ANAPC7 (reaction)
  • Reactome Reaction: ANAPC2 → ANAPC5 (reaction)
  • Reactome Reaction: UBE2E1 → ANAPC4 (reaction)
  • Reactome Reaction: ANAPC2 → CDC26 (reaction)
  • Reactome Reaction: ANAPC4 → ANAPC5 (reaction)
  • Reactome Reaction: PTTG1 → CDC16 (indirect_complex)
  • Reactome Reaction: PTTG1 → ANAPC4 (indirect_complex)
  • Reactome Reaction: ANAPC7 → CDC26 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC11 (reaction)
  • Reactome Reaction: CDC26 → UBB (reaction)
  • Reactome Reaction: CDC27 → ANAPC2 (reaction)
  • Reactome Reaction: CDC27 → ANAPC10 (reaction)
  • Reactome Reaction: CDC23 → CDC26 (reaction)
  • Reactome Reaction: ANAPC7 → ANAPC7 (reaction)
  • Reactome Reaction: CDC20 → CDC26 (reaction)
  • Reactome Reaction: ANAPC1 → UBC (reaction)
  • Reactome Reaction: CDC20 → CDC20 (reaction)
  • Reactome Reaction: PTTG1 → UBE2E1 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC10 (reaction)
  • Reactome Reaction: ANAPC11 → UBC (reaction)
  • Reactome Reaction: CDC26 → UBC (reaction)
  • Reactome Reaction: PTTG1 → RPS27A (reaction)
  • Reactome Reaction: CDC27 → RPS27A (reaction)
  • Reactome Reaction: CDC16 → CDC23 (reaction)
  • Reactome Reaction: PTTG1 → ANAPC2 (indirect_complex)
  • Reactome Reaction: ANAPC11 → ANAPC5 (reaction)
  • Reactome Reaction: PTTG1 → CDC23 (indirect_complex)
  • Reactome Reaction: PTTG1 → ANAPC7 (reaction)
  • Reactome Reaction: ANAPC2 → ANAPC7 (reaction)
  • Reactome Reaction: ANAPC11 → ANAPC2 (reaction)
  • Reactome Reaction: PTTG1 → CDC26 (reaction)
  • Reactome Reaction: UBE2E1 → CDC20 (reaction)
In total, 276 gene pairs are associated to this article in curated databases