Gene interactions and pathways from curated databases and text-mining
Cell reports 2013, PMID: 23972993

SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression.

Fukushima, Hidefumi; Ogura, Kohei; Wan, Lixin; Lu, Ying; Li, Victor; Gao, Daming; Liu, Pengda; Lau, Alan W; Wu, Tao; Kirschner, Marc W; Inuzuka, Hiroyuki; Wei, Wenyi

Proper cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key regulators by the anaphase-promoting complex (APC) and Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligase complexes. But precisely how APC and SCF activities are coordinated to regulate cell-cycle progression remains largely unclear. We previously showed that APC/Cdh1 earmarks the SCF component Skp2 for degradation. Here, we continue to report that SCF(β-TRCP) reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation. Furthermore, we define both cyclin A and Plk1, two well-known Cdh1 substrates, as upstream modifying enzymes that promote Cdh1 phosphorylation to trigger Cdh1 ubiquitination and subsequent degradation by SCF(β-TRCP). Thus, our work reveals a negative repression mechanism for SCF to control APC, thereby illustrating an elegant dual repression system between these two E3 ligase complexes to create the ordered cascade of APC and SCF activities governing timely cell-cycle transitions.

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Text Mining Data

SCF — APC/Cdh1: " Here, we continue to report that SCF ( ß-TRCP ) reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation "

SCF — APC/Cdh1: " Here, we continue to report that SCF ( ß-TRCP ) reciprocally controls APC/Cdh1 activity by governing Cdh1 ubiquitination and subsequent degradation "

Manually curated Databases

  • IRef Biogrid Interaction: FZR1 — SKP2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FZR1 — CCNA1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FZR1 — UBC (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: UBE2D1 — ANAPC11 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: FZR1 — PLK1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: FZR1 — PLK1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FZR1 — SOX2 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: FZR1 — SOX2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CDC34 — ANAPC11 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: FZR1 — BTRC (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FZR1 — CUL1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FZR1 — CDC27 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FZR1 — CDK2 (direct interaction, enzymatic study)
In total, 11 gene pairs are associated to this article in curated databases