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HPV E6 proteins interact with specific PML isoforms and allow distinctions to be made between different POD
Ernesto Guccione1, Katherine J Lethbridge, Neil Killick
1International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
Oncogene
|April 27, 2004
Summary
Human papillomaviruses (HPVs) E6 oncoproteins interact with promyelocytic leukemia (PML) nuclear bodies. This interaction destabilizes PML IV, enabling HPV to overcome cellular senescence.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- Mucosal human papillomaviruses (HPVs) cause various pathologies, including cervical cancers.
- The viral E6 protein is crucial for malignant progression, but its mechanism remains unclear.
Purpose of the Study:
- To analyze the intracellular distribution of E6 oncoproteins from HPV-18 and HPV-11.
- To investigate the interaction between HPV E6 proteins and promyelocytic leukemia (PML) protein isoforms.
Main Methods:
- Confocal microscopy to determine intracellular localization of E6 proteins.
- Co-immunoprecipitation to demonstrate in vivo interaction between E6 and PML isoforms.
- Proteasome inhibition assays to study PML destabilization.
Main Results:
- Both HPV-18 and HPV-11 E6 proteins localize to nuclear bodies, co-localizing with PML isoforms I-IV.
- HPV E6 proteins interact specifically with a subset of PML isoforms.
- HPV-18 E6 destabilizes PML IV via a proteasome-dependent pathway.
- Both HPV-11 and HPV-18 E6 overcome PML IV-induced cellular senescence.
Conclusions:
- HPV E6 oncoproteins target specific PML isoforms, suggesting separable functions for these isoforms.
- The interaction between HPV E6 and PML plays a role in viral oncogenesis by affecting cellular senescence.