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Aurora kinase-A inactivates DNA damage-induced apoptosis and spindle assembly checkpoint response functions of p73.

Elevated Aurora kinase-A expression is correlated with abrogation of DNA damage-induced apoptotic response and mitotic spindle assembly checkpoint (SAC) override in human tumor cells. We report that Aurora-A phosphorylation of p73 at serine235 abrogates its transactivation function and causes cytoplasmic sequestration in a complex with the chaperon protein mortalin. Aurora-A phosphorylated p73 also facilitates inactivation of SAC through dissociation of the MAD2-CDC20 complex in cells undergoing mitosis. Cells expressing phosphor-mimetic mutant (S235D) of p73 manifest altered growth properties, resistance to cisplatin- induced apoptosis, as well as premature dissociation of the MAD2-CDC20 complex, and accelerated mitotic exit with SAC override in the presence of spindle damage. Elevated cytoplasmic p73 in Aurora-A overexpressing primary human tumors corroborates the experimental findings.

Pubmed ID: 22340593


  • Katayama H
  • Wang J
  • Treekitkarnmongkol W
  • Kawai H
  • Sasai K
  • Zhang H
  • Wang H
  • Adams HP
  • Jiang S
  • Chakraborty SN
  • Suzuki F
  • Arlinghaus RB
  • Liu J
  • Mobley JA
  • Grizzle WE
  • Wang H
  • Sen S


Cancer cell

Publication Data

February 14, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: 5P30CA0101955
  • Agency: NCI NIH HHS, Id: CA16872
  • Agency: NCI NIH HHS, Id: P20 CA101955
  • Agency: NCI NIH HHS, Id: P30 CA016672
  • Agency: NCI NIH HHS, Id: P50 CA101955
  • Agency: NCI NIH HHS, Id: R01 CA089716
  • Agency: NCI NIH HHS, Id: R01 CA089716-06
  • Agency: NCI NIH HHS, Id: R01 CA089716-07
  • Agency: NCI NIH HHS, Id: R01 CA089716-08
  • Agency: NCI NIH HHS, Id: R01CA089716
  • Agency: NCI NIH HHS, Id: U01 CA111302
  • Agency: NCI NIH HHS, Id: U01CA111302

Mesh Terms

  • Apoptosis
  • Aurora Kinase A
  • Aurora Kinases
  • DNA Damage
  • DNA-Binding Proteins
  • HSP70 Heat-Shock Proteins
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Nuclear Proteins
  • Pancreatic Neoplasms
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins