Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Reexamination Certificate
2002-09-18
2008-10-14
Mondesi, Robert B. (Department: 1656)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
C435S006120, C530S300000, C424S001650
Reexamination Certificate
active
07435555
ABSTRACT:
A target asparagine residue of HIF 1 alpha and 2 alpha is hydroxylated at high oxygen tension to render HIF as a weak transcription factor. An asparagine hydroxylase hydroxylation motif and binding motif is proposed. A method of screening for agonists or antagonists of an asparagine hydroxylase is also proposed and involves mixing peptides or proteins having the hydroxylation and or the binding motif with asparagine hydroxylase and a candidate agonist or antagonist. The extent of inhibition or enhancement of binding; level of asparagine hydroxylation or transactivation may be measured depending on the nature of the protein or peptide. Additionally altered proteins resistant to hydroxylation are described as are nucleic acids encoding such proteins.
REFERENCES:
Linke et al., “Substrate requirements of the oxygen-sensing asparaginyl hydroxylase factor-inhibiting hypoxia-inducible factor”, Journal of Biological Chemistry 279: 14391-14397 (2004).
Hewitson, Kirsty S. et al., “Hypoxia-inducible Factor (HIF) Asparagine Hydroxylase is Identical to Factor Inhibiting HIF and is Related to the Cupin Structural Family,” J. of Biological Chemistry (Jul. 19, 2002) 277 (29) pp. 26351-26355.
William, Carsten et al., “Peptide blockade of HIF α degradation modulates cellular metabolism and angiogenesis,” Proceedings of the Nat. Acad. of Sci. of the United States of America (Aug. 6, 2002) 99 (16) pp. 10423-10428.
Groulx, Isabelle et al., “Oxygen-Dependent Ubiquitination and Degradation of Hypoxia-Inducible Factor Requires Nuclear-Cytoplasmic Trafficking of the von Hippel-Lindau Tumor Suppressor Protein,” Molecular and Cellular Bio., (Aug. 2002) 22 (15) pp. 5319-5336.
Dames, Sonja A. et al., “Structural basis for Hif-lα/CBP recognition in the cellular hypoxic response,” Proceedings of the Nat. Acad. of Sci. of the United States of America (Apr. 16, 2002) 99 (8) pp. 5271-5276.
Jaakola, P. et al., “Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O2-Regulated Prolyl Hydroxylation,” Science (Apr. 20, 2001) 292 (5516) pp. 468-472.
Gorman Jeffrey J
Lando David
Linke Sarah
Peet Daniel J
Whitelaw Murray L
Adelaide Research and Innovation Pty Ltd.
Coleman Henry D.
Desai Anand U.
Mondesi Robert B.
Sapone William J.
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