التفاصيل البيبلوغرافية
| العنوان: |
Aurora Kinase-A Inactivates DNA Damage-Induced Apoptosis and Spindle Assembly Checkpoint Response Functions of p73 |
| المؤلفون: |
Katayama, Hiroshi1, Wang, Jin1, Treekitkarnmongkol, Warapen1, Kawai, Hidehiko2, Sasai, Kaori1, Zhang, Hui1, Wang, Hua3, Adams, Henry P.4, Jiang, Shoulei1, Chakraborty, Sandip N.1, Suzuki, Fumio2, Arlinghaus, Ralph B.1, Liu, Jinsong3, Mobley, James A.5,6, Grizzle, William E.6,7, Wang, Huamin3, Sen, Subrata1 ssen@mdanderson.org |
| المصدر: |
Cancer Cell. Feb2012, Vol. 21 Issue 2, p196-211. 16p. |
| مصطلحات موضوعية: |
*AURORA kinases, *DNA damage, *APOPTOSIS, *GENE expression, *CISPLATIN, *TUMOR proteins, *MOLECULAR oncology |
| مستخلص: |
Summary: 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. [Copyright &y& Elsevier] |
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