Charakterisierung des zellulären Faktors PBF (Papillomavirus binding factor)

人类乳头瘤病毒(HPV)的组织和细胞类型特异性是在病毒基因转录水平上决定的，在HPV感染皮肤的情况下，这一点几乎没有研究。我们已经确定了一种新的细胞蛋白“乳头瘤病毒结合因子”(PBF)，它是一种与某些PV型的调节区相结合的转录因子。我们可以将PBF定性为细胞生长抑制因子，它在缺乏生长因子的情况下移位到细胞核中，其中PBF可以抑制转录。此外，PBF作为细胞因子RUNX1的合作伙伴，可能在皮肤乳头瘤病毒的组织特异性基因表达中发挥作用。在拟议的项目中，我们希望定义PBF介导的生长抑制的性质和机制，以及通过翻译后修饰对PBF活性的调节。对PBF和RUNX1与其合作伙伴RUNX1的功能相互作用的分析将阐明PBF和RUNX1在HPV基因表达调控中的作用。这些实验将有助于了解PBF在细胞内的功能以及对光伏生命周期的调控。

The tissue and cell type specificity of human papillomaviruses (HPV) is determined at the level of transcription of the viral genes, which is barely studied in the case of HPVs infecting the skin. We have identified the novel cellular protein “Papillomavirus binding factor” (PBF) as a transcription factor binding to the regulatory regions of certain PVtypes. We could characterize PBF as inhibitor of cell growth, which translocates into the nucleus upon lack of growth factors, where PBF can repress transcription. Moreover, PBF acts as cooperation partner for the cellular factor RUNX1, which may play a role in tissue specific gene expression of cutaneous papillomaviruses. In the proposed project we want to define the nature and the mechanisms of PBF-mediated growth suppression, as well as the regulation of PBF activity by post-translational modifications. The analysis of the functional interaction with its cooperation partner RUNX1 will elucidate the role of PBF and RUNX1 in regulation of HPV gene expression. These experiments will contribute to understand the function of PBF within the cell and in regulation of PV-life cycle.