Aurora-A Oncogene in Human Ovarian Cancer

Abstract

During past year, we have demonstrated that the Aurora-A interacts with and phosphorylates p53 tumor suppressor at serine-215 leading to abrogation of p53 DNA-binding and transactivation activity. Downstream target genes of p53, such as p21 and PTEN, were inhibited by Aurora-A in a Ser-215 phosphorylation-dependent manner. As a result, Aurora-A overrides the apoptosis and cell cycle arrest induced by cisplatin and gamma-irradiation, respectively. Our data indicate that phosphorylation of p53 at Ser-215 by Aurora-A is a major mechanism to inactivate p53. We have also shown that ectopic expression of Aurora-A induces chemoresistance in ovarian cancer cells. Further, Aurora-A inhibits BAX conformation change by inactivation of JNK and activation of Akt. In addition, we have identified 4 potential Aurora-A inhibitors by screening of a Small Focus chemical compound library.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Nov 01, 2005
Accession Number
ADA446899

Entities

People

  • Jin Q. Cheng
  • Santo V. Nicosia

Organizations

  • University of South Florida

Tags

DTIC Thesaurus Topics

  • Acetic Acid
  • Amino Acids
  • Apoptosis
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Inhibitors
  • Neoplasms
  • Ovarian Cancer
  • Peptides
  • Phosphoamino Acids
  • Programmed Cell Death
  • Two Dimensional

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics