Medical Importance of the PPP Family

The discovery that eukaryotic Ppp1 and Ppp2 are potently inhibited by naturally occurring toxins and tumor promoters, such as okadaic acid and microcystin, brought this group of enzymes to the attention of the general public, and the importance of protein serine/threonine phosphatases to the study of medicine was highlighted when it was discovered that Ppp3c (PP2B /calcinceurin) was the target of the widely used immunosuppressive drugs cyclosporin and FK506 (see Chapter 101). In addition, DNA tumor viruses (SV40 and polyoma virus) and HIV-1 have been shown to compromise the function of PP2A by producing proteins that compete with specific regulatory subunits [17]. Somewhat similarly, the dsRNA virus herpes simplex produces PP1-binding proteins that recruit Ppp1c from host cell complexes in order to enhance its own replication and evade host cell defense mechanisms [25].

Acknowledgments

The author thanks Philip Cohen for critical reading of the manuscript, David Campbell and Tamas Zeke for database sequence searches, and the Medical Research Council U.K. for financial support.

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