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Gene interactions and pathways from curated databases and text-mining
Oncogene 2005, PMID: 15782130

BARD1 induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase.

Feki, Anis; Jefford, Charles Edward; Berardi, Philip; Wu, Jian-Yu; Cartier, Laetitia; Krause, Karl-Heinz; Irminger-Finger, Irmgard

The BRCA1-associated RING domain protein BARD1 acts with BRCA1 in double-strand break repair and ubiquitination. BARD1 plays a role as mediator of apoptosis by binding to and stabilizing p53, and BARD1-repressed cells are resistant to apoptosis. We therefore investigated the mechanism by which BARD1 induces p53 stability and apoptosis. The apoptotic activity of p53 is regulated by phosphorylation. We demonstrate that BARD1 binds to unphosphorylated and serine-15 phosphorylated forms of p53 in several cell types and that the region required for binding comprises the region sufficient for apoptosis induction. In addition, BARD1 binds to Ku-70, the regulatory subunit of DNA-PK, suggesting that the mechanism of p53-induced apoptosis requires BARD1 for the phosphorylation of p53. Upregulation of BARD1 alone is sufficient for stabilization of p53 and phosphorylation on serine-15, as shown in nonmalignant epithelial cells and ovarian cancer cells, NuTu-19, which are defective in apoptosis induction and express aberrant splice variants of BARD1. Stabilization and phosphorylation of p53 in NuTu-19 cells, as well as apoptosis, can be induced by the exogenous expression of wild-type BARD1, suggesting that BARD1, by binding to the kinase and its substrate, catalyses p53 phosphorylation.

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Text Mining Data

p53 → BARD1: " We therefore investigated the mechanism by which BARD1 induces p53 stability and apoptosis "

p53 → BARD1: " In addition, BARD1 binds to Ku-70, the regulatory subunit of DNA-PK, suggesting that the mechanism of p53 induced apoptosis requires BARD1 for the phosphorylation of p53 "

p53 → BARD1: " Upregulation of BARD1 alone is sufficient for stabilization of p53 and phosphorylation on serine-15, as shown in nonmalignant epithelial cells and ovarian cancer cells, NuTu-19, which are defective in apoptosis induction and express aberrant splice variants of BARD1 "

p53 → BARD1: " Stabilization and phosphorylation of p53 in NuTu-19 cells, as well as apoptosis, can be induced by the exogenous expression of wild-type BARD1 , suggesting that BARD1, by binding to the kinase and its substrate, catalyses p53 phosphorylation "

Manually curated Databases

  • IRef Bind Interaction: BARD1 — TP53
  • IRef Bind Interaction: XRCC6 — TP53
  • IRef Bind Interaction: XRCC6 — BARD1
  • IRef Bind_translation Interaction: BARD1 — TP53 (coimmunoprecipitation)
  • IRef Bind_translation Interaction: XRCC6 — TP53 (coimmunoprecipitation)
  • IRef Bind_translation Interaction: XRCC6 — BARD1 (coimmunoprecipitation)
  • IRef Biogrid Interaction: BARD1 — TP53 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: XRCC6 — TP53 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: XRCC6 — BARD1 (physical association, affinity chromatography technology)
  • MIPS CORUM P53-BARD1-Ku70 complex: P53-BARD1-Ku70 complex complex (BARD1-TP53-XRCC6)
  • IRef Corum Interaction: Complex of TP53-XRCC6-BARD1-XRCC6-TP53-BARD1 (association, coimmunoprecipitation)
  • IRef Hprd Interaction: BARD1 — TP53 (in vivo)
  • IRef Hprd Interaction: XRCC6 — TP53 (in vivo)
  • IRef Hprd Interaction: XRCC6 — BARD1 (in vivo)
  • IRef Intact Interaction: BARD1 — TP53 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: XRCC6 — TP53 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: XRCC6 — BARD1 (physical association, anti bait coimmunoprecipitation)
  • NCI Pathway Database BARD1 signaling events: BARD1 (BARD1) → DNA-PK complex (PRKDC-XRCC5-XRCC6) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database BARD1 signaling events: BARD1 (BARD1) → BARD1/DNA-PK complex (BARD1-PRKDC-XRCC6-XRCC5) (modification, collaborate)
    Evidence: assay, physical interaction
  • NCI Pathway Database BARD1 signaling events: DNA-PK complex (PRKDC-XRCC5-XRCC6) → BARD1/DNA-PK complex (BARD1-PRKDC-XRCC6-XRCC5) (modification, collaborate)
    Evidence: assay, physical interaction
In total, 12 gene pairs are associated to this article in curated databases