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The product of the cph oncogene is a truncated, nucleotide-binding protein that enhances cellular survival to stress

Oncogene volume 18, pages 689–701 (1999)Cite this article

Abstract

Cph was isolated from neoplastic Syrian hamster embryo fibroblasts initiated by 3-methylcholanthrene (MCA), and was shown to be a single copy gene in the hamster genome, conserved from yeast to human cells, expressed in fetal cells and most adult tissues, and acting synergistically with H-ras in the transformation of murine NIH3T3 fibroblasts. We have now isolated Syrian hamster full-length cDNAs for the cph oncogene and proto-oncogene. Nucleotide sequence analysis revealed that cph was activated in MCA-treated cells by a point-mutational deletion at codon 214, which caused a shift in the normal open reading frame (ORF) and brought a translation termination codon 33 amino acids downstream. While proto-cph encodes a protein (pcph) of 469 amino acids, cph encodes a truncated protein (cph) of 246 amino acids with a new, hydrophobic C-terminus. Similar mechanisms activated cph in other MCA-treated Syrian hamster cells. The cph and proto-cph proteins have partial sequence homology with two protein families: GDP/GTP exchange factors and nucleotide phosphohydrolases. In vitro translated, gel-purified cph proteins did not catalyze nucleotide exchange for H-ras, but were able to bind nucleotide phosphates, in particular ribonucleotide diphosphates such as UDP and GDP. Steady-state levels of cph mRNA increased 6.7-fold in hamster neoplastic cells, relative to a 2.2-fold increase in normal cells, when they were subjected to a nutritional stress such as serum deprivation. Moreover, cph-transformed NIH3T3 cells showed increased survival to various forms of stress (serum starvation, hyperthermia, ionizing radiation), strongly suggesting that cph participates in cellular mechanisms of response to stress.

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Acknowledgements

This work was supported by US Public Health Service grant CA64472 from the National Cancer Institute. Densitometry was performed at the Lombardi Cancer Center's Macromolecular Synthesis and Sequencing Shared Resource which is supported in part by US Public Health Service Grant P30-CA-51008. Tumorigenicity assays were supported by intramural funds from the Radiation Medicine Department of the Georgetown University Medical Center.

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  1. Department of Radiation Medicine, Georgetown University Medical Center, Washington, 20007, DC, USA

    Juan A Velasco, Matias A Avila & Vicente Notario

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Velasco, J., Avila, M. & Notario, V. The product of the cph oncogene is a truncated, nucleotide-binding protein that enhances cellular survival to stress. Oncogene 18, 689–701 (1999). https://doi.org/10.1038/sj.onc.1202324

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