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Papillomaviruses (PV) are the causative agents of warts, papillomas and cervical cancer. The viral regulatory protein E2 is the major coordinator of viral nucleic acid metabolism. For bovine, as well as for human PV-s, in addition to full-length E2 shorter repressorforms are described. These repressorforms do not contain an E2 transactivation domain (TAD), which is required for most of the E2 activities. The repressorforms share the DNA binding domain (DBD) with full-length E2. E2 (full-length and repressors) dimerises through the common DBD. In case of bovine PV (BPV) it has been shown that the truncated (artificial) form of E2 with different length forms heterodimers. So, also the full-length E2 may form heterodimers with its repressors. The ratio of the full-length E2 to repressors has been measured only in case of BPV. The exact ratio depends on the cell-line and group, however, the level of repressors is in any case at least 10 times higher than the level of the full-length E2. So, if the formation of homo- and heterodimers occurs with the same efficiency, the major form of full-length E2 is its heterodimer with repressors. Until now the role and function of the heterodimers is not well understood (and also not studied), despite the fact that in the absence of the repressors the BPV and HPV31 failed to maintain their genomes as episomal plasmids. The aim of the current study is to find out the functions and biochemical activities of the E2 heterodimers and repressors to explain their role in viral life-cycle. As a model for heterodimers we plan to use an E2 polypeptide where the extra DBD is fused to the C-terminus of the full-length E2. Such polypeptide forms pseudodimeric and functional DBD and, like a native E2 heterodimer, contains only a single TAD. In this way we shall overcome the difficulties arising in case of coexpressing full-length and repressor forms (simultaneous presence of heterodimers and two type of homodimers)and get a lot of new information on fuctioning of E2 heterodimers. |