The high-risk HPV E6 target scribble (hScrib) is required for HPV E6 expression in cervical tumour-derived cell lines

Area of Science:

• Molecular biology
• Oncology
• Virology

Background:

• High-risk HPV E6 oncoproteins target PDZ domain-containing proteins, crucial for viral life cycle and malignant transformation.
• PDZ proteins, often tumor suppressors controlling cell polarity, can gain oncogenic functions upon mislocalization or overexpression.
• hDlg and hScrib are key E6 targets implicated in these processes.

Purpose of the Study:

• To investigate the role of hScrib in maintaining HPV-18 E6 protein levels in HeLa cells.
• To elucidate the cooperative function of hScrib and E6 in cervical tumor-derived cell lines.
• To understand the impact on protein translation and oncogenic signaling pathways.

Main Methods:

• Analysis of hScrib expression and its effect on HPV-18 E6 protein stability, transcription, and translation in HeLa cells.
• Investigation of the S6 kinase signaling pathway activation in cervical tumor-derived cell lines.
• Assessment of the interplay between hScrib and E6 in regulating protein synthesis.

Main Results:

• hScrib expression is essential for maintaining high levels of HPV-18 E6 protein in HeLa cells.
• Loss of hScrib reduces E6 transcription and translation rates but does not affect E6 stability.
• hScrib and E6 cooperate to activate the S6 kinase pathway, enhancing protein translation in cervical cancer cell lines.

Conclusions:

• Residual hScrib in HPV-transformed cells exhibits pro-oncogenic activity.
• The study highlights the dual functions of E6 targets involved in cell polarity.
• Targeting the hScrib-E6 interaction could offer therapeutic strategies for HPV-associated cancers.