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 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.
Boese
A
A
Department of Virology, Building 47, University of the Saarland Medical School, D-66421 Homburg/Saar, Germany.
Sauter
M
M
Galli
U
U
Best
B
B
Herbst
H
H
Mayer
J
J
Kremmer
E
E
Roemer
K
K
Mueller-Lantzsch
N
N
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001665:Binding Sites; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020077:Endogenous Retroviruses / Q000235:genetics*; D018237:Germinoma / Q000276:immunology / Q000821:virology; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016335:Zinc Fingers
D000914:Antibodies, Viral; D004268:DNA-Binding Proteins; C406149:HERV-K cORF protein, Human endogenous retrovirus K; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; D014764:Viral Proteins; C513267:Zbtb16 protein, mouse; C092037:ZBTB16 protein, human