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

Papillomavirus Research
Christian KranjecLawrence Banks

Abstract

The ability of high-risk HPV E6 oncoproteins to target cellular proteins which harbor PDZ domains is believed to play an important role in the virus life cycle and to influence the ability of these viruses to bring about malignant transformation. Whilst many of these PDZ proteins are potential tumour suppressors, involved in the control of cell polarity and cell-contact, recent studies suggest that mislocalisation or overexpression might result in the emergence of oncogenic functions. This has been shown most clearly for two E6 targets, hDlg and hScrib. In this study we show that hScrib plays such a role in HeLa cells, where its expression is required for maintaining high levels of HPV-18 E6 protein. Loss of hScrib has no effect on E6 stability but results in lower levels of E6 transcription and a reduced rate of E6 translation. We further show that, in the context of cervical tumour-derived cell lines, both hScrib and E6 cooperate in the activation of the S6 kinase signaling pathway, and thereby contribute towards maintaining high rates of protein translation. These results indicate that the residual hScrib that is present within HPV transformed cells is pro-oncogenic, and highlights the dual functions of E6 cell polarity targ...Continue Reading

Citations

Sep 6, 2018·International Journal of Molecular Sciences·Abida SiddiqaLawrence Banks
Feb 28, 2019·The Journal of General Virology·Vanessa Sarabia-Vega, Lawrence Banks
Oct 18, 2018·Nature Communications·Marianna MadeoPaola D Vermeer
May 28, 2019·Frontiers in Oncology·Tarik Gheit
Sep 3, 2019·Frontiers in Cell and Developmental Biology·Jesse M YoungMichelle A Ozbun
Oct 2, 2020·Oncogene·Marie-Josée SantoniJean-Paul Borg
Jan 12, 2021·The Journal of General Virology·James A ScarthAndrew Macdonald
Mar 16, 2021·Tumour Virus Research·Arushi VatsLawrence Banks
May 10, 2021·Journal of Gynecology Obstetrics and Human Reproduction·Mohammad AbbasFarzana Mahdi
Jul 25, 2020·Protein and Peptide Letters·Rabbiah Manzoor MalikMohammad Amjad Kamal

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