Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73

Hiroshi Katayama, Jin Wang, Warapen Treekitkarnmongkol, Hidehiko Kawai, Kaori Sasai, Hui Zhang, Hua Wang, Henry P. Adams, Shoulei Jiang, Sandip N. Chakraborty, Fumio Suzuki, Ralph B. Arlinghaus, Jinsong Liu, James A. Mobley, William E. Grizzle, Huamin Wang, Subrata Sen

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)196-211
Number of pages16
JournalCancer Cell
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 14 2012

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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