Author/Authors :
Katayama، نويسنده , , Hiroshi and Wang، نويسنده , , Jin and Treekitkarnmongkol، نويسنده , , Warapen and Kawai، نويسنده , , Hidehiko and Sasai، نويسنده , , Kaori and Zhang، نويسنده , , Hui and Wang، نويسنده , , Hua and Adams، نويسنده , , Henry P. and Jiang، نويسنده , , Shoulei and Chakraborty، نويسنده , , Sandip N. and Suzuki، نويسنده , , Fumio and Arlinghaus، نويسنده , , Ralph B. and Liu، نويسنده , , Jinsong and Mobley، نويسنده , , James A. and Grizzle، نويسنده , , William S-Y. Wang، نويسنده , , Huamin and Sen، نويسنده , , Subrata، نويسنده ,
Abstract :
Summary
ed 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.
