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About the Authors:
James J. Fiordalisi
Affiliation: Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Brian J. Dewar
Affiliation: Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Lee M. Graves
Affiliations Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
James P. Madigan
Affiliation: Curriculum in Genetics & Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Adrienne D. Cox
* E-mail: [email protected]
Affiliations Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Curriculum in Genetics & Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Introduction
Extensive evidence has accumulated linking the putative tyrosine phosphatase PRL-3 with invasion and metastasis (reviewed in [1]–[3]). Although the precise roster of its substrates remains to be fully determined, it is clear that PRL-3 mediated biological activities require its phosphatase activity and its lipid modification by farnesylation, as mutation of the catalytic residue C104 or the prenylated CAAX motif abrogates these functions [4]–[8]. However, little is known concerning the mechanism(s) through which PRL-3 itself is regulated, and it has largely been assumed that both its biochemical and biological activity correlate solely with its expression. Numerous studies have examined relative PRL-3 expression levels in cancer versus normal cells or tissues [1]–[3]. Other studies have demonstrated, for example, control of PRL-3 transcription by p53 [9], Snail [10], or MEF2C [11]; PCBP1-mediated control of PRL-3 translation [12]; and FKBP38-mediated control of PRL-3 protein stability [13]. One possible mechanism of regulation other than expression levels is post-translational modification of PRL-3, such as...