HPV16 E6 controls the gap junction protein Cx43 in cervical tumour cells

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)

[img]
Preview
Text
112832.pdf - Published Version
Available under License Creative Commons Attribution.

5MB

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
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hodgins, Dr Malcolm and Graham, Professor Sheila and Johnstone, Dr Scott and MacDonald, Dr Alasdair and Edward, Dr Michael
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 > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Viruses
Publisher:M D P I AG
ISSN:1999-4915
ISSN (Online):1999-4915
Copyright Holders:Copyright © 2015 The Authors
First Published:First published in Viruses 7(10):5243-5256
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
438191The role of the hD1g, ZO-1 and hScrib tumour suppressors in control of Cx43 gap junctional intercellular communication in HPV-associated tumourigenesis.Sheila GrahamAssociation for International Cancer Research (AICR)08-0159MVLS III - CENTRE FOR VIRUS RESEARCH