Sun, P., Dong, L., MacDonald, A. I., Akbari, S., Edward, M., Hodgins, M. B., Johnstone, S. R. and Graham, S. V. (2015) HPV16 E6 controls the gap junction protein Cx43 in cervical tumour cells. Viruses, 7(10), pp. 5243-5256. (doi: 10.3390/v7102871) (PMID:26445057) (PMCID:PMC4632379)
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Abstract
Human papillomavirus type 16 (HPV16) causes a range of cancers including cervical and head and neck cancers. HPV E6 oncoprotein binds the cell polarity regulator hDlg (human homologue of Drosophila Discs Large). Previously we showed in vitro, and now in vivo, that hDlg also binds Connexin 43 (Cx43), a major component of gap junctions that mediate intercellular transfer of small molecules. In HPV16-positive non-tumour cervical epithelial cells (W12G) Cx43 localised to the plasma membrane, while in W12T tumour cells derived from these, it relocated with hDlg into the cytoplasm. We now provide evidence that E6 regulates this cytoplasmic pool of Cx43. E6 siRNA depletion in W12T cells resulted in restoration of Cx43 and hDlg trafficking to the cell membrane. In C33a HPV-negative cervical tumour cells expressing HPV16 or 18 E6, Cx43 was located primarily in the cytoplasm, but mutation of the 18E6 C-terminal hDlg binding motif resulted in redistribution of Cx43 to the membrane. The data indicate for the first time that increased cytoplasmic E6 levels associated with malignant progression alter Cx43 trafficking and recycling to the membrane and the E6/hDlg interaction may be involved. This suggests a novel E6-associated mechanism for changes in Cx43 trafficking in cervical tumour cells.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Hodgins, Dr Malcolm and Graham, Professor Sheila and Edward, Dr Michael and Johnstone, Dr Scott and MacDonald, Dr Alasdair |
Authors: | Sun, P., Dong, L., MacDonald, A. I., Akbari, S., Edward, M., Hodgins, M. B., Johnstone, S. R., and Graham, S. V. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
Journal Name: | Viruses |
Publisher: | M D P I AG |
ISSN: | 1999-4915 |
ISSN (Online): | 1999-4915 |
Published Online: | 05 October 2015 |
Copyright Holders: | Copyright © 2015 The Authors |
First Published: | First published in Viruses 7(10):5243-5256 |
Publisher Policy: | Reproduced under a Creative Commons License |
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