| Literature DB >> 22340593 |
Hiroshi Katayama1, 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.
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. Copyright ÂEntities:
Mesh：
Substances：
Year: 2012 PMID： 22340593 PMCID： PMC3760020 DOI： 10.1016/j.ccr.2011.12.025
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743