Cellular and Intraviral Interaction Partners of Papillomavirus E6 Protein

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dc.contributor.advisor Stehle, Thilo (Prof. Dr.)
dc.contributor.author Lim, Jia Wen
dc.date.accessioned 2023-09-22T10:11:31Z
dc.date.available 2023-09-22T10:11:31Z
dc.date.issued 2023-09-22
dc.identifier.uri http://hdl.handle.net/10900/145908
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1459085 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-87249
dc.description.abstract Papillomaviruses are small DNA tumor viruses that infect humans and animals. Persistent infection with high-risk alpha-HPV can develop into cervical and anogenital cancer. HPV16, the most carcinogenic high-risk alpha type, causes >50% of HPV-associated cervical cancers. In addition, cutaneous beta HPV is highly associated with skin cancer in patients with epidermodysplasia verruciformis and individuals with immunosuppression. The carcinogenic E6 and E7 proteins are the major contributors to HPV-associated cancers. They are known to disrupt numerous cellular proteins and signaling pathways essential for tumor suppression. Cottontail rabbit papillomavirus (CRPV) induces papillomas in rabbit skin. It is an established animal model for HPV-mediated carcinogenesis, in which the viral E6 protein plays a critical role. Studies have shown that cutaneous beta-HPV, bovine PV, and mouse PV E6 proteins associate with mastermind-like 1 protein (MAML1) and subsequently inhibit Notch signaling, thereby impairing cell differentiation and proliferation. However, CRPV E6 differs from other E6 proteins in that it encodes an extended E6 protein (long E6, LE6) and an N-terminally truncated product (short E6, SE6). In this work, we describe the interaction between CRPV E6 proteins and MAML1 and their ability to down-regulate Notch signaling, which may be a way CRPV infection induces carcinogenesis similar to beta-HPV. The E6 protein interacts with cellular proteins to disrupt the cellular signaling pathway and can cooperate with E7 proteins to immortalize keratinocytes. The roles of E6 and E7 in the HPV life cycle and the development of carcinogenesis have previously been studied independently. However, a direct interaction between E6 and E7 has yet to be shown. In this thesis, a direct interaction between the E6 and E7 proteins of HPV16 and HPV31 is demonstrated in cell-based assays and verified using biophysical methods. In addition, the involvement of two E7 molecules and two E6 molecules in complex formation was demonstrated by analytical ultracentrifugation. Furthermore, the fluorescence polarization assay showed the binding affinity of the complexes is in a micromolar range. This interaction raises questions about the function of the complex in carcinogenesis and in the viral life cycle that requires further investigation. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podno de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en en
dc.subject.classification Papillomaviren de_DE
dc.subject.ddc 570 de_DE
dc.subject.other Protein-protein interaction en
dc.subject.other E6 protein en
dc.subject.other E7 protein en
dc.subject.other cottontail rabbit en
dc.subject.other Notch signaling en
dc.title Cellular and Intraviral Interaction Partners of Papillomavirus E6 Protein en
dc.type PhDThesis de_DE
dcterms.dateAccepted 2023-01-31
utue.publikation.fachbereich Biochemie de_DE
utue.publikation.fakultaet 7 Mathematisch-Naturwissenschaftliche Fakultät de_DE
utue.publikation.noppn yes de_DE

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