Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells.
The zinc finger protein ZPR1 is present in the cytoplasm of quiescent mammalian cells and translocates to the nucleus upon treatment with mitogens, including epidermal growth factor (EGF). Homologues of ZPR1 were identified in yeast and mammals. These ZPR1 proteins bind to eukaryotic translation elongation factor-1alpha (eEF-1alpha). Studies of mammalian cells demonstrated that EGF treatment induces the interaction of ZPR1 with eEF-1alpha and the redistribution of both proteins to the nucleus. In the yeast Saccharomyces cerevisiae, genetic analysis demonstrated that ZPR1 is an essential gene. Deletion analysis demonstrated that the NH2-terminal region of ZPR1 is required for normal growth and that the COOH-terminal region was essential for viability in S. cerevisiae. The yeast ZPR1 protein redistributes from the cytoplasm to the nucleus in response to nutrient stimulation. Disruption of the binding of ZPR1 to eEF-1alpha by mutational analysis resulted in an accumulation of cells in the G2/M phase of cell cycle and defective growth. Reconstitution of the ZPR1 interaction with eEF-1alpha restored normal growth. We conclude that ZPR1 is essential for cell viability and that its interaction with eEF-1alpha contributes to normal cellular proliferation.
Gangwani
L
L
Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Mikrut
M
M
Galcheva-Gargova
Z
Z
Davis
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D016384:Consensus Sequence; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D016195:G2 Phase; D017353:Gene Deletion; D005800:Genes, Fungal; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008322:Mammals; D026901:Membrane Transport Proteins; D051379:Mice; D008938:Mitosis; D008969:Molecular Sequence Data; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D016335:Zinc Fingers
D002352:Carrier Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; C490986:ZPR1 protein, S cerevisiae; C099746:ZPR1 protein, human; C490987:Zfp259 protein, mouse