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© The Rockefeller University Press, 0021-9525/1998//1471 $5.00
The Journal of Cell Biology, Volume 143, Number 6, , 1998 1471-1484


Article

Interaction of ZPR1 with Translation Elongation Factor-1{alpha} in Proliferating Cells



Laxman Gangwani, Monique Mikrut, Zoya Galcheva-Gargova, and Roger J. Davis

Howard Hughes Medical Institute and Program in Molecular Medicine, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605

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-1{alpha} (eEF-1{alpha}). Studies of mammalian cells demonstrated that EGF treatment induces the interaction of ZPR1 with eEF-1{alpha} 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-1{alpha} 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-1{alpha} restored normal growth. We conclude that ZPR1 is essential for cell viability and that its interaction with eEF-1{alpha} contributes to normal cellular proliferation.

Key Words: cell cycle • eEF-1{alpha} • EGF • Saccharomyces cerevisiae • zinc finger



Abbreviations used in this paper: CBP, calmodulin-binding protein; CT, COOH-terminal region of ZPR1; cZPR1, S. cerevisiae ZPR1; DAPI, 4'6-diamidino-2-phenylindole; eEF-1{alpha}, eukaryotic translation elongation factor-1{alpha}; GFP, green fluorescent protein; GST, glutathione-S-transferase; mZPR1, mouse ZPR1; NT, NH2-terminal region of ZPR1; PMA, phorbol 12-myristate 13-acetate; PVDF, polyvinylene difluoride; pZPR1, S. pombe ZPR1.



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