Marek's disease virus Meq transforms chicken cells via the v-Jun transcriptional cascade: a converging transforming pathway for avian oncoviruses.
Marek's disease virus (MDV) is a highly pathogenic and oncogenic herpesvirus of chickens. MDV encodes a basic leucine zipper (bZIP) protein, Meq (MDV EcoQ). The bZIP domain of Meq shares homology with Jun/Fos, whereas the transactivation/repressor domain is entirely different. Increasing evidence suggests that Meq is the oncoprotein of MDV. Direct evidence that Meq transforms chicken cells and the underlying mechanism, however, remain completely unknown. Taking advantage of the DF-1 chicken embryo fibroblast transformation system, a well established model for studying avian sarcoma and leukemia oncogenes, we probed the transformation properties and pathways of Meq. We found that Meq transforms DF-1, with a cell morphology akin to v-Jun and v-Ski transformed cells, and protects DF-1 from apoptosis, and the transformed cells are tumorigenic in chorioallantoic membrane assay. Significantly, using microarray and RT-PCR analyses, we have identified up-regulated genes such as JTAP-1, JAC, and HB-EGF, which belong to the v-Jun transforming pathway. In addition, c-Jun was found to form stable dimers with Meq and colocalize with it in the transformed cells. RNA interference to Meq and c-Jun down-modulated the expression of these genes and reduced the growth of the transformed DF-1, suggesting that Meq transforms chicken cells by pirating the Jun pathway. These data suggest that avian herpesvirus and retrovirus oncogenes use a similar strategy in transformation and oncogenesis.
Levy
Alon M
AM
Department of Biological Chemistry, School of Medicine, University of California, Davis, CA 95616, USA.
Gilad
Oren
O
Xia
Liang
L
Izumiya
Yoshihiro
Y
Choi
Jonathan
J
Tsalenko
Anya
A
Yakhini
Zohar
Z
Witter
Richard
R
Lee
Lucy
L
Cardona
Carol J
CJ
Kung
Hsing-Jien
HJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000166:cytology; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D008381:Herpesvirus 2, Gallid / Q000235:genetics* / Q000378:metabolism; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008156:Luciferases; D046228:Microarray Analysis; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
C100369:Eco-Q protein, Gallid herpesvirus 2; D009856:Oncogene Proteins, Viral; D034741:RNA, Small Interfering; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases