Methods of evaluating phosphatase inhibitors

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

Reexamination Certificate

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C435S195000, C536S023200, C536S023500

Reexamination Certificate

active

10493057

ABSTRACT:
The present invention identified OVARC1000473 (SEQ ID NO: 1) and NT2RM1000377 (SEQ ID NO: 3) as clones showing suppression of CREB activation by forskolin, and provides evaluation methods using these genes, and/or proteins encoded by these genes. Furthermore, these proteins were found to enhance cell damage. Compounds that can be screened based on the evaluation methods of this invention are useful as agents for inhibiting the CREB dephosphorylation reaction, agents for suppressing enhancement of cell damage, and preventive and therapeutic agents for memory disorders and/or neurodegenerative disorders.

REFERENCES:
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Cohen P. T. W. Two isoforms of protein phosphatase 1 may be produced from the same gene, FEBS Letters, 1988, 232, 17-23.
Alignment of SEQ ID No. 4 with protein Accession No. AAB94018.
Alignment of SEQ ID No. 4 with human protein Accession No. Q9H9Z5.
Hagiwara M. et al., Transcriptional attenuation following cAMP induction requires PP-1-mediated dephosphorylation of CREB., Cell, vol. 70, No. 1, pp. 105-113 1992.
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Be Wadzinski et al., Nuclear protein phosphatase 2A dephosphorylates protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. Molecular and Cellular Biology, vol. 13, No. 5, pp. 2822-2834 1993.
WH Wheat et al., Simian virus 40 small tumor antigen inhibits dephosphorylation of protein kinase A-phosphorylated CREB and regulates CREB transcriptional stimulation. Molecular and Cellular Biology, vol. 14, No. 9, pp. 5881-5890 1994.
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