Autophagy regulates UBC9 levels during viral-mediated tumorigenesis
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View abstract on PubMed
Summary
This summary is machine-generated.Human papillomavirus (HPV) infection increases UBC9 levels, promoting cancer by blocking cell death. HPV oncoproteins disrupt autophagy, leading to UBC9 accumulation and viral oncogenesis.
Area Of Science
- Oncology
- Virology
- Cellular Biology
Background
- UBC9 is crucial for SUMOylation and cellular functions, with altered expression in cancers.
- UBC9 expression increases during early stages of human papillomavirus (HPV)-mediated cervical lesions.
- Understanding how viral oncoproteins exploit UBC9 is vital for cancer research.
Purpose Of The Study
- To investigate UBC9 dysregulation in HPV-driven head and neck tumorigenesis.
- To elucidate the mechanisms of UBC9 deregulation in an oncoviral context.
- To identify the role of UBC9 and autophagy in HPV oncogenesis.
Main Methods
- Analysis of human samples and HPV-infected pre-cancerous tissues.
- Use of primary human keratinocytes as the host for HPV.
- Employing ultrastructural, pharmacological, and genetic approaches.
- Investigating the impact of HPV E6/E7 oncoproteins on autophagy and UBC9 levels.
Main Results
- HPV drives UBC9 up-regulation in early head and neck tumorigenesis.
- UBC9 overexpression enhances host cell resistance to apoptosis.
- HPV E6/E7 oncoproteins inhibit autophagosome-lysosome fusion, a key step in autophagy.
- This inhibition leads to p53-dependent UBC9 accumulation during HPV-induced transformation.
Conclusions
- HPV oncoproteins manipulate UBC9 levels to promote cancer development.
- HPV E6/E7 interfere with the autophagic degradation pathway of UBC9.
- UBC9 and autophagy are identified as novel hallmarks of HPV-related oncogenesis.
- Targeting UBC9 and autophagy presents potential therapeutic strategies for HPV-related malignancies.
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