A. Boese et al., Human endogenous retrovirus protein cORF supports cell transformation and associates with the promyelocytic leukemia zinc finger protein, ONCOGENE, 19(38), 2000, pp. 4328-4336
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.