Abstract
In order to adapt to and to cope with an often hostile host environment, many viruses have evolved to encode products that are homologous to cellular proteins. These proteins exploit the existing host machinery and allow viruses to readily integrate into the host functional network. As a result, viruses are able to maneuver their journey seemingly effortlessly inside the host cell to achieve ultimate survival. Such molecular mimicries sometime go overboard, allowing viruses to overtake the cellular pathways or evade the immune system as do many of the retroviral oncogenes. Retroviral oncogenes are derived directly from host genes, and they are virtually identical to host genes in sequences except those mutations that make them unregulatable by host. Oncogenic herpesviruses also encode oncogenes, or transforming genes, which have independently evolved and are distantly related to host genes. However, these genes do share consensus structural motifs with cellular genes involved in cell growth and apoptosis and are functional analogues to host genes. The Marek's disease virus oncoprotein, MEQ, is one such example. MEQ is a basic region-leucine zipper (bZIP) transactivator which shares extensive homology with the Jun/Fos family of transcription factors within the bZIP domain, but not in other regions. Like all other bZIP proteins, MEQ is capable of dimerizing with itself and with a variety of bZIP partners including c-Jun, B-Jun, c-Fos, CREB, ATF-1, ATF-2, and SNF. MEQ-Jun heterodimers bind to a TRE/CRE-like sequence in the meq promoter region and have been shown to up-regulate MEQ expression in both chicken embryo fibroblasts and F9 cells. In addition, the bZIP and transactivation domains are interchangeable between MEQ and c-Jun in terms of transforming potential; i.e. MEQ can functionally substitute for c-Jun. These properties enable MEQ to engage in host cell processes by disguising itself as c-Jun. On the other hand, there are properties of MEQ notably different from c-Jun, which include its capability to bind RNA, to bind a CACAC-bent DNA structure as a homodimer, to inhibit apoptosis, and to interact with CDK2. MEQ’s subcellular localization in the nucleolus and coiled body, is also different from Jun/Fos family of transactivators. These unique features may provide the MEQ with additional facility in regulating MDV replication, establishing latency, and cellular transformation. In this review, we will attempt to summarize the past research progress on MDV meq, with a focused on the similarities and differences between MEQ and cellular proteins, and between MEQ and other viral oncoproteins.
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Liu, JL., Kung, HJ. Marek's Disease Herpesvirus Transforming Protein MEQ: a c-Jun Analogue with an Alternative Life Style. Virus Genes 21, 51–64 (2000). https://doi.org/10.1023/A:1008132313289
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DOI: https://doi.org/10.1023/A:1008132313289