Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Reexamination Certificate
2008-04-15
2008-04-15
Yu, Misook (Department: 1642)
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
C435S007100
Reexamination Certificate
active
07358335
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.
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Halvorson Mark
The Trustees of Columbia University in the City of New York
Wilmer Cutler Pickering Hale and Dorr LLP
Yu Misook
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