ARF-BP1 as mediator of p53-dependent and independent tumor suppression and uses thereof
US7358335B2 · kind B2 · utility
Assignee
Inventor
Key dates
| Filing date | Apr 29, 2005 |
| Grant date | Apr 15, 2008 |
| Priority date | — |
| Expiry date | Apr 29, 2025 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC12N9/93
- WIPO fieldMeasurement
- WIPO sectorInstruments
Abstract
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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.