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Title: THE NUCLEOLAR AND NUCLEAR LOCALIZATION PROPERTIES OF A HERPESVIRAL BZIP ONCOPROTEIN, MEQ

Author
item LIU, JUINN-LIN - CASE WESTERN RESERVE UNIV
item Lee, Lucy
item YE, YING - CLEVELAND CLINIC FOUNDATI
item KUNG, HSING-JIEN - CASE WESTERN RESERVE UNIV

Submitted to: Journal of Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/15/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Marek's disease virus (MDV) causes malignant lymphoma (cancer) in chickens. The research goal is to identify the heredity material (genes) which may be involved in cancer induction. The approach we used was to identify a gene which has some motif or characteristics resemble other cancer causing genes in chickens. We have identified Meq gene to be a putative gene for induction of Marek's disease. In this paper, we localized the product (protein) of Meq gene using antiserum specific for Meq. The Meq protein is localized in the nucleolus and the coiled bodies of the cancer cells. This information is important in that it points to the function of Meq as a potential gene regulator for MDV.

Technical Abstract: Marek's disease virus (MDV) is one of the most oncogenic herpesviruses and induces T lymphomas in chickens within weeks after infection. Only a limited number of viral transcripts are detected in MDV tumor samples and cell lines. One of the major transcripts encodes MEQ, a 339 aa bZIP protein which is homologous to the jun/fos family of transcription factors. The C-terminal half of MEQ contains proline-rich repeats which, when fused to the yeast DNA-binding domain Ga14 (residues 1-147), exhibits transactivation function. MEQ can dimerize with itself and with c-jun. The MEQ/c-jun heterodimers bind to an AP-1-like enhancer within the MEQ promoter region with greater affinity than do homodimers of either protein, and transactivate MEQ expression. Here we show that MEQ is expressed in the nucleus, but interestingly, with a predominant fraction in the nucleoli and coiled bodies. This makes MEQ the first bZIP protein to be identified in the nucleoli. MEQ contains two stretches of basic residues, designated as basic region 1 (BR1) and basic region 2 (BR2). Using a series of deletion mutants, we have mapped the primary nuclear localization signal (NLS), and the sole nucleolar localization signal (NoLS) to the BR2 region. BR1 was shown to provide an auxiliary signal in nuclear translocation. To demonstrate that BR2 is an authentic NoLS,BR2 was fused to cytoplasmic v-raf (delta gag) kinase. The BR2-raf fusion protein was observed to migrate into the nucleoplasm and the nucleolus. The BR2 region can be further divided into two long arginine/lysine stretches, BR2N and BR2C, which are separated by the five amino acids Asn-Arg-Asp-Ala-Ala (NRDAA).