The proposed project is designed to assess the feasibility of producing for commercial application; Several inhibitors of the serine/threonine (ser/thr) protein phosphatases which demonstrate specificity towards specific types of protein phosphatases. One particular extract has already been demonstrated to have activity which inhibits only type 1 protein phosphatase. To date five ser/thr protein phosphatase types have been biochemically identified and they are known to play a role in the physiological regulation of a variety of biological phenomena ranging from gene transcription to cell division to muscle contraction. Currently the only known inhibitors of these phosphatases are non-specific, either inhibiting 4 of the 5 se/thr protein phosphatases or inhibiting other enzymes as well (i.e. protein kinases). The ser/thr protein phosphatase inhibitors we propose to purify are potentially vastly superior to current inhibitors because their activity is directed to only one protein phosphatase. Several extracts containing inhibitors of AP-1 mediated gene transcription have been identified. Gene transcription through AP-1 is known to involve the fos/jun proto oncogenes and to be associated with cell proliferation and carcinogenesis. The inhibitors of transcriptional activation have application for the research community as well as potential therapeutic use for proliferative diseases.
Ser/thr protein phosphatase inhibitors and inhibitors of AP-1 mediated gene expression will be of tremendous benefit to the research community as tools for studying specific physiologic functions and diseases. Potential pharmacologic use of these inhibitors is also possible for specific proliferative disorders such as cancer.
