アイテム詳細

要旨

Cervical cancer is the second most common cancer among women worldwide.Every year approximately 500.000 new cases are diagnosed and 270.000 women die from this malignancy. The tumor is caused by a persistent infection with high-risk human papillomaviruses (HPV). The recently developed vaccination prevents infections with high-risk HPV 16 and HPV 18, two of the most frequent virus types. Nevertheless, there are several unsolved problems: The vaccination does not cover all high risk HPV types, there is no effective treatment for infected women available and the vaccine is still not sufficiently available in the most severely affected regions, in developing countries. Therefore, an antiviral therapy would be highly desirable. During papillomaviral infections the viral genomes are tethered to mitotic chromosomes to pass the infection on to the next generation of cells during replication. For this maintenance mechanism the viral E2 protein binds to the cellular bromodomain protein Brd4. Our previous work has also established that the Brd4-E2 interaction is involved in viral transcriptional regulation mechanisms, which are involved in cervical cancer pathogenesis. The goal of the presented work is to analyze and further characterize the protein-protein interaction networks underlying these genome maintenance mechanisms and thereby to gain additional insights into the mitotic complexes involved. Furthermore, we are working on the development of target-specific anti - HPV drugs and will discuss the impact for the prevention of cervical cancer.