Anthrax lethal factor is a MAPK kinase protease

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving hydrolase

Reexamination Certificate

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C435S221000

Reexamination Certificate

active

06893835

ABSTRACT:
The present invention relates to in vitro and ex vivo methods of screening for modulators, homologues, and mimetics of lethal factor mitogen activated protein kinase kinase (MAPKK) protease activity, as well as methods of treating cancer by administering LF to transformed cells.

REFERENCES:
Vitale G. et al., Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor, Biochem. J. 2000, 352, 739-745.*
Duesbery, Nicholas S., et al. “Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor,”Science280:734-737 (May 1, 1998).
Duesbery, Nick S., et al. “CENP-E is an essential kinetochore motor in maturing oocytes and is masked during Mos-dependent, cell cycle arrest at metaphase II,”Pro. Natl. Acad. Sci. USA94:9165-9170 (Aug. 1997).
Kimpel, Kurt R., et al. “Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity,”Molecular Microbiology13(6):1093-1100 (1994).
Koo, Han-Mo, et al. “Enhanced Sensitivity to 1-β-D-Arabinofuranosylcytosine and Topoisomerase II Inhibitors in Tumor Cell Lines Harboring Activated ras Oncogenes,”Cancer Research56:5211-5216 (Nov. 15, 1996).
Menard, Armelle, et al. “The cytotoxic activity ofBacillus anthracislethal factor is inhibited by leukotriene A4hydrolase and metallopeptidase inhibitors,”Biochem. J.320:687-691 (1996).
Weinstein, John N., et al. “An Information-Intensive Approach to the Molecular Pharmcology of Cancer,”Science275:343-349 (Jan. 17, 1997).

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