This invention provides nucleic acids, polypeptides, peptide fragments, antibodies and methods of using an alternative reading frame of the Ink4a locus (ARF). Also provided are domains involved in the interaction between ARF and Hdm2. ARF encodes a potent tumor suppressor protein that interacts with the regulator protein Hdm2 to induce p53 mediated cell cycle arrest. ARF is a potential prodrug for cancer therapy as well as a useful screening target for anti-cancer drug design and discovery.
Tumor suppressor, cancer therapy, cancer drug, screening target, ARF, Hdm2, p53
Granted Patents or Published Applications
U.S. Patent Nos. 2,233,144; 5,723,313; 5,876,965; 6,172,194; 6,407,062; 6,482,929; 6,586,203
Related Scientific References
Sherr C. J., Weber J. D. “The ARF/p53 pathway” Curr. Opin. Genet. Dev. 10:94-99 (2000);
Weber J. D., et. al. “p53-independent functions of the p19ARF tumor suppressor” Genes Dev. 14:2358-2365 (2000);
Quelle D.E. et. al. “Alternative reading frames of the INK4a tumor suppressor gene encode unrelated proteins capable of inducing cell cycle arrest” Cell 83(6): 993-1000 (1995);
Bothner, B. et al., “Peptides derived from two dynamically disordered proteins self-assemble into amyloid-like fibrils”, J. Am. Chem. Soc. 125(11):3200-3201 (March 2003).
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