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

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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
Externally publishedYes

Fingerprint

Aurora Kinase A
M Phase Cell Cycle Checkpoints
DNA Damage
Apoptosis
Mitosis
Cisplatin
Transcriptional Activation
Neoplasms
Phosphorylation
Growth
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73. / Katayama, Hiroshi; Wang, Jin; Treekitkarnmongkol, Warapen; Kawai, Hidehiko; Sasai, Kaori; Zhang, Hui; Wang, Hua; Adams, Henry P.; Jiang, Shoulei; Chakraborty, Sandip N.; Suzuki, Fumio; Arlinghaus, Ralph B.; Liu, Jinsong; Mobley, James A.; Grizzle, William E.; Wang, Huamin; Sen, Subrata.

In: Cancer Cell, Vol. 21, No. 2, 14.02.2012, p. 196-211.

Research output: Contribution to journalArticle

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 2012, 'Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73', Cancer Cell, vol. 21, no. 2, pp. 196-211. https://doi.org/10.1016/j.ccr.2011.12.025
Katayama, Hiroshi ; Wang, Jin ; Treekitkarnmongkol, Warapen ; Kawai, Hidehiko ; Sasai, Kaori ; Zhang, Hui ; Wang, Hua ; Adams, Henry P. ; Jiang, Shoulei ; Chakraborty, Sandip N. ; Suzuki, Fumio ; Arlinghaus, Ralph B. ; Liu, Jinsong ; Mobley, James A. ; Grizzle, William E. ; Wang, Huamin ; Sen, Subrata. / Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73. In: Cancer Cell. 2012 ; Vol. 21, No. 2. pp. 196-211.
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