Anisomelic acid promotes proteasomal degradation of HPV16 E6 via E3 ligase recruitment: A mass spectrometry-based interactome study
- J Proteomics. 2026 Jan 6:322:105536. doi: 10.1016/j.jprot.2025.105536.
- 1. Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland. Electronic address: [email protected].
- 2. Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland.
- 3. Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; School of Medicine, Medical Sciences and Nutrition, Aberdeen University, Aberdeen, UK.
- 4. Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; InFLAMES Research Flagship Center, Åbo Akademi University, 20520 Turku, Finland.
- 5. Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, 20520 Turku, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520 Turku, Finland; Euro-Bioimaging, ERIC, 20520 Turku, Finland. Electronic address: [email protected].
Human papillomavirus (HPV) is a major driver of cervical and Other epithelial cancers, with the viral oncoprotein E6 playing a central role in tumorigenesis by promoting degradation of the tumor suppressor p53. While prophylactic vaccines prevent Infection, there remains a critical need for therapeutic strategies that eliminate established HPV-positive cells. Here, we identify anisomelic acid (AA), a natural diterpenoid, as a novel pharmacological principle that selectively induces the degradation of HPV16 E6. Using cellular thermal shift assay, we demonstrate that AA directly interacts with E6, likely triggering a conformational change that promotes its ubiquitination. Proteomic analysis of the E6 interactome in AA-treated cells revealed consistent enrichment of E3 ubiquitin ligases, including E6AP, UBR4, CDC20, and TRIP12, as well as proteasomal subunits. To our knowledge, this represents the first comprehensive proteomics framework of the HPV16 E6 interactome under small-molecule treatment conditions. These findings support a model in which AA facilitates proteasome-mediated elimination of E6, and the dataset itself provides a timely and valuable resource for HPV biology and therapeutic development.