In a study published in the mBio Journal of the American Society for Microbiology, collaborators disclose significant implications in the understanding of HPV-associated cancers.
17 December 2024: Researchers from the Tumour Virology and Functional Cell Biology Laboratories at ICGEB, Trieste, Italy, the Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago Illinois, USA, and the School of Cardiovascular & Metabolic Medicine and Sciences, King’s College London, UK, Providing deeper insights into the intricate interplay between viral proteins and host cellular machinery and the development of targeted therapies they identify a potential target for therapeutic strategies against Human Papillomavirus (HPV)-associated cancers.
Cervical cancer is one of the most common types of cancer, affecting approximately 500,000 women worldwide. A small subset of human papillomavirus (HPV) types, known as the high-risk HPV types (mainly HPV-16 and -18), are the causative agents of cervical cancer and a large number of other human malignancies. Persistent expression of the HPV E6 and E7 oncoproteins leads to the development of cancer and is a major hallmark of high-risk HPV-induced carcinogenesis.
Dr. Arushi Vats, first author of the publication explains: “HPV, the leading cause of cervical cancer, uses the E6 oncoprotein to degrade p53, a key tumor suppressor. While E6 is stabilized by the ubiquitin ligase E6AP, this study is the first to identify FBXO4 as a novel regulator that targets E6 for degradation in the absence of E6AP. Strikingly, the simultaneous depletion of E6AP and FBXO4 in HPV-positive cancer cells induced p53-dependent cell death, uncovering a critical interplay between these proteins.” She concludes: “This discovery reveals an entirely new layer of E6 regulation and highlights FBXO4 as a potential target for therapeutic strategies against HPV-associated cancers.”
Link to Article:
Regulation of Human Papillomavirus E6 oncoprotein function via a novel ubiquitin ligase FBXO4
