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Title: BIOLOGICAL PROPERTIES OF THE MAREK'S DISEASE LATENT PROTEIN MEQ: SUBCELLULAR LOCALIZATION AND TRANSFORMING POTENTIAL

Author
item LIU, JUINN-LIN - CASE WESTERN RESERVE UNIV
item Lee, Lucy
item KUNG, HSING-JIEN - CASE WESTERN RESERVE UNIV

Submitted to: International Marek's Disease Symposium Abstracts and Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 9/7/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Like other herpesviral oncogenes and/or latent proteins, the transcripts of MEQ (MDV Eco Q) of the Marek's disease virus are consistently detected in MDV-induced tumors and cell lines. We recently verified that indeed MEQ proteins are abundantly and ubiquitously expressed in the MDV- transformed cell lines. In this report, we showed that MEQ proteins are predominantly localized to the nucleoplasm, the nucleolus and the coiled bodies. The major nuclear localization signal (NLS) and the sole nucleolar localization signal (NoLS) have been mapped to the basic region 2 (BR2). The BR1, on the other hand, provides a supplementary signal for nuclear entry. We also provide direct evidence to support the notion that MEQ is one of the oncogenes in the MDV. Transformation of Rat-2 cells can be achieved if MEQ was delivered by retroviral infection and overexpressed. When expressed at a lower level (as was the case in cells transfected with MEQ DNA), MEQ-mediated transformation requires a complementing oncogene such as v-ras. We found that bZIP domain is absolutely essential for transformation. For full transforming activity, both the C-terminal transactivation domain and the N-terminal region are also required. The bZIP and transactivation domains are interchangeable between MEQ and c-jun. Finally, MEQ is able to maximize its transforming potential by antagonizing apoptosis of Rat-2 cells. Taken together, our studies suggest that MEQ may carry out its transforming and anti-apoptotic functions through its transregulation of host gene expression. Conversely, the expression of MEQ in the nucleolus and coiled bodies may provide new leads to uncovering other novel properties beyond its transcriptional potential.