发明名称 |
ARF-BP1 AS MEDIATOR OF P53-DEPENDENT AND INDEPENDENT TUMOR SUPPRESSION AND USES THEREOF |
摘要 |
<p>The present invention relates to the mechanism of ARF-mediated cell growth suppression. ARF-BP1 is identified as a novel ubiquitin ligase, and a major component of ARF-containing nuclear complexes in human cells. The present invention discloses a novel mechanism of ARF-mediated p53 activation and that ARF-BP1 is a critical mediator of both p53-independent and p53-dependent tumor suppression functions of ARF. Inactivation of ARF-BP1 in normal cells stabilizes p53 and induces p53-dependent apoptosis. Inactivation of ARF-BP1, but not Mdm2, in p53-wildtype cells promotes cell growth inhibition in a manner reminiscent of ARF induction. ARF-BP1 directly binds and ubiquitinates p53 and inactivation of endogenous ARF-BP1 is crucial for ARF-mediated p53 stabilization in Mdm2-null cells. ARF-BP1 is advantageous over Mdm2 as a target for suppressing tumor cell growth regardless of p53 status.</p> |
申请公布号 |
WO2006031928(A2) |
申请公布日期 |
2006.03.23 |
申请号 |
WO2005US32835 |
申请日期 |
2005.09.15 |
申请人 |
THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OFNEW YORK;GU, WEI |
发明人 |
GU, WEI |
分类号 |
C12Q1/68;C07H21/04;C12N9/64;C12P21/06;G01N33/574 |
主分类号 |
C12Q1/68 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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