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  • Original Paper
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Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein

Oncogene volume 19, pages 4328–4336 (2000)Cite this article

Abstract

Human endogenous retrovirus sequences (HERVs) reside in the genomes of primates and humans for several million years. The majority of HERVs is non-coding but a limited set is intact and can express proteins. We have recently identified an almost intact HERV-K(HML-2) provirus on chromosome 7 and have documented that most patients with germ cell tumors (GCTs) display antibodies directed against proteins of HERV-K(HML-2). To address whether these proteins merely represent tumor markers or contribute to neoplastic transformation, we examined the transforming potential of various HERV sequences and studied physical interactions between HERV and cellular proteins by yeast two-hybrid and biochemical assays. cORF, a protein encoded by the C-terminal open reading frame within the env gene, supports tumor growth in nude mice and associates with the promyelocytic leukemia zinc finger protein (PLZF). The interaction domains map between amino acid residues 21 and 87 of cORF, and between residues 245 and 543 of PLZF. PLZF is critical for spermatogenesis in mice. Abnormal spermatogenesis or maturation of gonocytes is thought to predispose humans to the development of germ cell tumors. Thus, cORF of human endogenous retroviruses may contribute to tumor development by interfering with processes during spermatogenesis that involve PLZF.

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Acknowledgements

We are grateful to Roger Brent and Jonathan Licht for materials and to Reinhard Maier and Stefan Theis for help with software application. This work was supported in part by grants from the German Research Foundation (DFG) to K Roemer (SFB399-B5) and N Mueller-Lantzsch (SFB399-B2).

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Author notes

  1. K Roemer and N Mueller-Lantzsch: K Roemer and N Mueller-Lantzschare are equal senior authors

Authors and Affiliations

  1. Department of Virology, Building 47, University of the Saarland Medical School, Homburg/Saar, D-66421, Germany

    A Boese, M Sauter, U Galli, B Best, J Mayer, K Roemer & N Mueller-Lantzsch

  2. Gerhard-Domagk-Institut for Pathology, Domagk Str. 17, Münster, D-48149, Germany

    H Herbst

  3. GSF-Forschungszentrum für Umwelt und Gesundheit, Institut für Molekulare Immunologie, Marchioninistr. 25, München, D-81377, Germany

    E Kremmer

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Boese, A., Sauter, M., Galli, U. et al. Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein. Oncogene 19, 4328–4336 (2000). https://doi.org/10.1038/sj.onc.1203794

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