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Title: TRANSFORMING POTENTIAL OF A HERPESVIRAL ONCOPROTEIN MEQ: MORPHOLOGICAL TRANSFORMATION, SERUM-INDEPENDENT GROWTH AND INHIBITION OF APOPTOSIS

Author
item KUNG, H - CASE WESTERN RESERVE
item LIU, J - CASE WESTERN RESERVE
item Lee, Lucy

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary: Interpretive Summary Marek's disease remains a major problem in the commercial poultry industry. The purpose of this research was to demonstrate that MEQ, a Marek's disease virus gene, resembles another gene family with the property of inducing tumors. We found MEQ product is abundantly produced in Marek's disease virus tumor cell lines. When we cloned MEQ gene into a rat gene cell line, we found over production of MEQ product in rat cells. This resulted in uncontrolled cell growth, which resembled that of cancer cells. This report is the first evidence that a Marek's disease gene may be causing cancer in chickens. This MEQ gene will be the first targeted for removal with the hope of creating a Marek's disease virus without cancer producing capabilities. Such a virus would be used to create a vaccine to protect against Marek's disease. Success here would have a tremendous impact on the poultry industry by reducing losses due to Marek's disease.

Technical Abstract: Marek's disease virus (MDV) induces the rapid development of overwhelming T-cell lymphomas in chickens. One of its candidate oncogenes, MEQ (MDV EcoQ) 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. Over-expression of MEQ results in transformation of a rodent fibroblast cell line, RAT-2. The criteria of transformation 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 TNF-alpha, C2-Ceramide, UV irradiation and serum deprivation. Its anti-apoptotic function requires new protein synthesis, as treatment with a protein synthesis inhibitor, cycloheximide, partially reversed MEQ's anti-apoptotic 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 antagonized apoptosis through regulation of its downstream target genes involved in apoptotic and/or anti-apoptotic pathways.