Nuclear localization of protein phosphatase 5 is dependent on the carboxy-terminal region.
Endogenous and overexpressed protein phosphatase 5 (PP5) localizes to the nucleus and cytoplasm of HeLa cells, while the overexpressed TPR domain of PP5 is restricted to the cytoplasm. Deletion and mutational analysis of human PP5 demonstrates that the C-terminal amino acids 420-499 are essential for nuclear localization and PP5 activity is not required. Since the phosphatase domain terminates at 473, these studies suggest that the highly conserved section (476-491) with the eukaryotic consensus FXAVPHPXPhiXPMAYAN is required for nuclear localization of PP5. Bacterially expressed PP5 is inhibited by several tumor promoters but not by the anticancer drug fostriecin.
Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, MSI/WTB Complex, University of Dundee, Dow Street, DD1 5EH, Scotland, Dundee, UK.
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Borthwick
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Cohen
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000475:Alkenes / Q000494:pharmacology; D019943:Amino Acid Substitution; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D016384:Consensus Sequence; D017124:Conserved Sequence / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011090:Polyenes; D017434:Protein Structure, Tertiary / Q000235:genetics; D011753:Pyrones; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000475:Alkenes; D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D002273:Carcinogens; D008164:Luminescent Proteins; D009687:Nuclear Proteins; D011090:Polyenes; D011753:Pyrones; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5; C040313:fostriecin