The Japan Radiation Research Society Annual Meeting Abstracts
The 50th Annual Meeting of The Japan Radiation Research Society
Session ID : CP-110
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Radiation Response and Signal Transduction
Mechanism of suppressive effect of sodium orthovanadate on p53
*Shinichi YAMAMOTOAkinori MORITAAzusa ITOAtsushi ENOMOTOAoshihisa MATSUMOTOOsamu FUNATSUYoshio HOSOINorio SUZUKIMasahiko IKEKITA
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CONFERENCE PROCEEDINGS FREE ACCESS

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Abstract
The tumor suppressor p53 protects the cell against cancer by inducing apoptosis in response to multiple stresses. Some 50% of human cancers have mutations or deletions in the gene for p53 that inactivate or impair its apoptotic potential. On the other hand, in cancer therapy, p53 causes severe side effects by inducing excessive apoptotic death in several normal tissues. Thus, p53 inhibitory drugs have been suggested to rescue the acute response to cancer therapy. In this respect, recent studies have shown transcription-independent p53-mediated apoptosis via mitochondria. These findings indicate that effective p53 inhibitors should suppress both transcription-dependent and -independent pathways. We have reported a novel effect of sodium orthovanadate (vanadate) that inactivates p53 by inducing conformational change in it. Therefore, we investigated the effect of vanadate on the each pathways. We initially confirmed vanadate as an inhibitor of p53 transcription by luciferase reporter assay for its transcription and by immunoblotting of its transactivation. Furthermore, immunocoprecipitation analysis using anti-Bak, Bcl-2, and Bcl-xL antibodies demonstrated that vanadate suppressed the interaction of p53 with these Bcl-2 family proteins. Considering the evidence that these interacting proteins bind core domain of p53, vanadate may influence this domain, resulting in the inhibition of the binding of target genes and these protein partners.
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© 2007 The Japan Radiation Research Society
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