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Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells.

Gangwani L, Mikrut M, Galcheva-Gargova Z, Davis RJ - J. Cell Biol. (1998)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

ABSTRACT
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.

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Identification of ZPR1 homologues in mammals and  yeast. (A) The sequence of the S. cerevisiae, S. pombe, and mouse  ZPR1 proteins deduced from the nucleotide sequence of DNA  clones is presented. Residues identical to the sequence of mouse  ZPR1 are indicated with a period (.). Gaps were introduced into  the sequences to optimize the alignment (-). Overline, zinc fingers; asterisks, Cys residues. The sequences of mouse ZPR1, S.  pombe zpr1 and S. cerevisiae ZPR1 have been deposited with  GenBank/EMBL/DDBJ accession numbers U41287, AF019768  and AF019769, respectively. (B) Schematic representation of the  predicted domain structure of ZPR1. The regions required for interaction with the EGF receptor are indicated (EGF-R).
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Figure 1: Identification of ZPR1 homologues in mammals and yeast. (A) The sequence of the S. cerevisiae, S. pombe, and mouse ZPR1 proteins deduced from the nucleotide sequence of DNA clones is presented. Residues identical to the sequence of mouse ZPR1 are indicated with a period (.). Gaps were introduced into the sequences to optimize the alignment (-). Overline, zinc fingers; asterisks, Cys residues. The sequences of mouse ZPR1, S. pombe zpr1 and S. cerevisiae ZPR1 have been deposited with GenBank/EMBL/DDBJ accession numbers U41287, AF019768 and AF019769, respectively. (B) Schematic representation of the predicted domain structure of ZPR1. The regions required for interaction with the EGF receptor are indicated (EGF-R).

Mentions: Homologues of the mammalian zinc finger protein ZPR1 were identified and cloned from the yeast S. cerevisiae and Schizosaccharomyces pombe. The sequence of the mouse, S. cerevisiae and S. pombe ZPR1 proteins was deduced from the nucleotide sequence of DNA clones (Fig. 1 A). Comparison of these ZPR1 proteins indicates a conserved structure including two similar zinc fingers (ZnF1 and ZnF2) and similar regions after each zinc finger (Fig. 1 B, A and B). The mouse ZPR1 (mZPR1) protein is 46% identical and 72% similar to S. cerevisiae ZPR1 (cZPR1) and 43% identical and 70% similar to S. pombe ZPR1 (pZPR1). The two yeast proteins are 55% identical and 78% similar. The high level of homology between yeast and mammalian ZPR1 suggests that the overall structure of the protein is conserved between lower and higher eukaryotes.


Interaction of ZPR1 with translation elongation factor-1alpha in proliferating cells.

Gangwani L, Mikrut M, Galcheva-Gargova Z, Davis RJ - J. Cell Biol. (1998)

Identification of ZPR1 homologues in mammals and  yeast. (A) The sequence of the S. cerevisiae, S. pombe, and mouse  ZPR1 proteins deduced from the nucleotide sequence of DNA  clones is presented. Residues identical to the sequence of mouse  ZPR1 are indicated with a period (.). Gaps were introduced into  the sequences to optimize the alignment (-). Overline, zinc fingers; asterisks, Cys residues. The sequences of mouse ZPR1, S.  pombe zpr1 and S. cerevisiae ZPR1 have been deposited with  GenBank/EMBL/DDBJ accession numbers U41287, AF019768  and AF019769, respectively. (B) Schematic representation of the  predicted domain structure of ZPR1. The regions required for interaction with the EGF receptor are indicated (EGF-R).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2132977&req=5

Figure 1: Identification of ZPR1 homologues in mammals and yeast. (A) The sequence of the S. cerevisiae, S. pombe, and mouse ZPR1 proteins deduced from the nucleotide sequence of DNA clones is presented. Residues identical to the sequence of mouse ZPR1 are indicated with a period (.). Gaps were introduced into the sequences to optimize the alignment (-). Overline, zinc fingers; asterisks, Cys residues. The sequences of mouse ZPR1, S. pombe zpr1 and S. cerevisiae ZPR1 have been deposited with GenBank/EMBL/DDBJ accession numbers U41287, AF019768 and AF019769, respectively. (B) Schematic representation of the predicted domain structure of ZPR1. The regions required for interaction with the EGF receptor are indicated (EGF-R).
Mentions: Homologues of the mammalian zinc finger protein ZPR1 were identified and cloned from the yeast S. cerevisiae and Schizosaccharomyces pombe. The sequence of the mouse, S. cerevisiae and S. pombe ZPR1 proteins was deduced from the nucleotide sequence of DNA clones (Fig. 1 A). Comparison of these ZPR1 proteins indicates a conserved structure including two similar zinc fingers (ZnF1 and ZnF2) and similar regions after each zinc finger (Fig. 1 B, A and B). The mouse ZPR1 (mZPR1) protein is 46% identical and 72% similar to S. cerevisiae ZPR1 (cZPR1) and 43% identical and 70% similar to S. pombe ZPR1 (pZPR1). The two yeast proteins are 55% identical and 78% similar. The high level of homology between yeast and mammalian ZPR1 suggests that the overall structure of the protein is conserved between lower and higher eukaryotes.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus