Transforming potential of the herpesvirus oncoprotein MEQ: morphological transformation, serum-independent growth, and inhibition of apoptosis.
Marek's disease virus (MDV) induces the rapid development of overwhelming T-cell lymphomas in chickens. One of its candidate oncogenes, meq (MDV Eco Q) which encodes a bZIP protein, has been biochemically characterized as a transcription factor. Interestingly, MEQ proteins are expressed not only in the nucleoplasm but also in the coiled bodies and the nucleolus. Its novel subcellular localization suggests that MEQ may be involved in other functions beyond its transcriptional potential. In this report we show that MEQ proteins are expressed ubiquitously and abundantly in MDV tumor cell lines. Overexpression of MEQ results in transformation of a rodent fibroblast cell line, Rat-2. The criteria of transformation are based on morphological transfiguration, anchorage-independent growth, and serum-independent growth. Furthermore, MEQ is able to distend the transforming capacity of MEQ-transformed Rat-2 cells through inhibition of apoptosis. Specifically, MEQ can efficiently protect Rat-2 cells from cell death induced by multiple modes including tumor necrosis factor alpha, C2-ceramide, UV irradiation, and serum deprivation. Its antiapoptotic function requires new protein synthesis, as treatment with a protein synthesis inhibitor, cycloheximide, partially reversed MEQ's antiapoptotic effect. Coincidentally, transcriptional induction of bcl-2 and suppression of bax are also observed in MEQ-transformed Rat-2 cells. Taken together, our results suggest that MEQ antagonizes apoptosis through regulation of its downstream target genes involved in apoptotic and/or antiapoptotic pathways.
Liu
J L
JL
Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4960, USA.
Ye
Y
Y
Lee
L F
LF
Kung
H J
HJ
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D002472:Cell Transformation, Viral; D002645:Chickens; D016895:Culture Media, Serum-Free; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D008381:Herpesvirus 2, Gallid / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D008380:Marek Disease / Q000209:etiology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D051381:Rats
D016895:Culture Media, Serum-Free; D017931:DNA Primers; C100369:Eco-Q protein, Gallid herpesvirus 2; D009856:Oncogene Proteins, Viral