Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition.

Aurora-A/BTAK/STK15 localizes to the centrosome in the G(2)-M phase, and its kinase activity regulates the G(2) to M transition of the cell cycle. Previous studies have shown that the BRCA1 breast cancer tumor suppressor also localizes to the centrosome and that BRCA1 inactivation results in loss of the G(2)-M checkpoint. We demonstrate here that Aurora-A physically binds to and phosphorylates BRCA1. Biochemical analysis showed that BRCA1 amino acids 1314-1863 binds to Aurora-A. Site-directed mutagenesis indicated that Ser(308) of BRCA1 is phosphorylated by Aurora-A in vitro. Anti-phospho-specific antibodies against Ser(308) of BRCA1 demonstrated that Ser(308) is phosphorylated in vivo. Phosphorylation of Ser(308) increased in the early M phase when Aurora-A activity also increases; these effects could be abolished by ionizing radiation. Consistent with these observations, acute loss of Aurora-A by small interfering RNA resulted in reduced phosphorylation of BRCA1 Ser(308), and transient infection of adenovirus Aurora-A increased Ser(308) phosphorylation. Mutation of a single phosphorylation site of BRCA1 (S308N), when expressed in BRCA1-deficient mouse embryo fibroblasts, decreased the number of cells in the M phase to a degree similar to that with wild type BRCA1-mediated G(2) arrest induced by DNA damage. We propose that BRCA1 phosphorylation by Aurora-A plays a role in G(2) to M transition of cell cycle.

Pubmed ID: 14990569


  • Ouchi M
  • Fujiuchi N
  • Sasai K
  • Katayama H
  • Minamishima YA
  • Ongusaha PP
  • Deng C
  • Sen S
  • Lee SW
  • Ouchi T


The Journal of biological chemistry

Publication Data

May 7, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: CA 79892
  • Agency: NCI NIH HHS, Id: CA 90631

Mesh Terms

  • Adenoviridae
  • Animals
  • Aurora Kinase A
  • Aurora Kinases
  • BRCA1 Protein
  • Binding Sites
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Separation
  • DNA Damage
  • Flow Cytometry
  • G2 Phase
  • Glutathione Transferase
  • Humans
  • Immunoblotting
  • Mitosis
  • Mutagenesis, Site-Directed
  • Mutation
  • Phosphorylation
  • Plasmids
  • Precipitin Tests
  • Protein Binding
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering
  • Radiation, Ionizing
  • Serine
  • Transfection
  • Xenopus Proteins