Charakterisierung des Humanen PapillomavirusE6 Protein

Abstract

Human Papillomaviruses comprise a large group of double-stranded DNA viruses which infect mucosal or cutaneous epithelial cells. Depending on the type of induced lesions, mucosal HPV viruses are classified into high risk and low risk types. Low risk HPV types induce the formation of benign genital warts. In contrast high risk HPV types can induce tumor formation e.g. cervical cancer. Cervical cancer is the second most common cancer among women worldwide and mucosal high risk HPV DNA can be found in 99% of all cervical cancers. Much is known about high risk HPV types and their actions in cells, whereas the modes of action of low risk HPV have not been elucidated.Using a yeast two hybrid screen, three new potential binding partners for low risk HPV11E6 were identified in this study, one of which is the first ever found specific interaction partner for HPV11E6 with no binding to HPV16E6 in vitro. Accumulation of HPV11E6 with the newly identified binding partner and anti-apoptitic protein HAX-1 was shown by confocal microscopy. Furthermore, we found that expression of HPV11E6 led to the formation of unidentified structures within cells, and the expression of SLIM facilitated degradation of HPV11E6 in cellulo.In this study, the PDZ domain containing proteins SLIM and LNX were identified as new interaction partners of the high risk HPV16E6, which were also ubiquitinated by the E6/E6AP complex. As a common characteristic for both HPV11E6 and 16E6 we found that binding to E6AP promotes stabilization of E6 providing reason to suggest the existence of a cellular E3 ligase specific for viral E6 proteins.