Gene interactions and pathways from curated databases and text-mining
Cell 2011, PMID: 21241890

Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner.

Song, Min Sup; Carracedo, Arkaitz; Salmena, Leonardo; Song, Su Jung; Egia, Ainara; Malumbres, Marcos; Pandolfi, Pier Paolo

PTEN is a frequently mutated tumor suppressor gene that opposes the PI3K/AKT pathway through dephosphorylation of phosphoinositide-3,4,5-triphosphate. Recently, nuclear compartmentalization of PTEN was found as a key component of its tumor-suppressive activity; however its nuclear function remains poorly defined. Here we show that nuclear PTEN interacts with APC/C, promotes APC/C association with CDH1, and thereby enhances the tumor-suppressive activity of the APC-CDH1 complex. We find that nuclear exclusion but not phosphatase inactivation of PTEN impairs APC-CDH1. This nuclear function of PTEN provides a straightforward mechanistic explanation for the fail-safe cellular senescence response elicited by acute PTEN loss and the tumor-suppressive activity of catalytically inactive PTEN. Importantly, we demonstrate that PTEN mutant and PTEN null states are not synonymous as they are differentially sensitive to pharmacological inhibition of APC-CDH1 targets such as PLK1 and Aurora kinases. This finding identifies a strategy for cancer patient stratification and, thus, optimization of targeted therapies. PAPERCLIP:

Diseases/Pathways annotated by Medline MESH: Prostatic Neoplasms
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Text Mining Data

APC-CDH1 → PTEN: " Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase independent manner "

APC-CDH1 → PTEN: " Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase independent manner "

CDH1 → PTEN: " Here we show that nuclear PTEN interacts with APC/C, promotes APC/C association with CDH1 , and thereby enhances the tumor-suppressive activity of the APC-CDH1 complex "

APC-CDH1 → PTEN: " Here we show that nuclear PTEN interacts with APC/C, promotes APC/C association with CDH1, and thereby enhances the tumor-suppressive activity of the APC-CDH1 complex "

APC-CDH1 ⊣ PTEN: " We find that nuclear exclusion but not phosphatase inactivation of PTEN impairs APC-CDH1 "

APC-CDH1 ⊣ PTEN: " We find that nuclear exclusion but not phosphatase inactivation of PTEN impairs APC-CDH1 "

Manually curated Databases

  • IRef Biogrid Interaction: CDC27 — ANAPC5 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: ANAPC4 — CDC27 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: FZR1 — CCNB1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: ANAPC7 — CDC27 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HIST1H1A — CCNE1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: CCNA2 — HIST1H1A (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: PTEN — ANAPC4 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: UBC — ETS2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PTEN — ANAPC5 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PTEN — FZR1 (direct interaction, pull down)
  • IRef Biogrid Interaction: PTEN — FZR1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PTEN — ANAPC7 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HIST1H1A — CDK2 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: FZR1 — CDC27 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PTEN — CDC27 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PTEN — CDC27 (direct interaction, pull down)
  • IRef Biogrid Interaction: CCNB1 — UBC (physical association, affinity chromatography technology)
  • IRef Intact Interaction: FZR1 — CDC27 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: PTEN — CDC27 (colocalization, fluorescence microscopy)
  • IRef Intact Interaction: PTEN — CDC27 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: PTEN — CDC27 (physical association, fluorescence microscopy)
  • IRef Intact Interaction: Complex of 16 proteins (association, anti bait coimmunoprecipitation)
In total, 18 gene pairs are associated to this article in curated databases