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

作者：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^*

来源：Cancer Cell, 2012, 21(2): 196-211.

DOI：10.1016/j.ccr.2011.12.025

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.

• 出版日期2012-2-14