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

Human endogenous retrovirus sequences (HERVs) reside in the genomes of prim ates and humans for several million years, The majority of HERVs is non-cod ing 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 antibod ies directed against proteins of HERV-K(HML-2), To address whether these pr oteins merely represent tumor markers or contribute to neoplastic transform ation, 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-termina l open reading frame within the cnv gene, supports tumor growth in nude mic e 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 spermatoge nesis in mice. Abnormal spermatogenesis or maturation of gonocytes is thoug ht to predispose humans to the development of germ cell tumors. Thus, cORF of human endogenous retroviruses may contribute to tumor development by int erfering,vith processes during spermatogenesis that involve PLZF.