Human papillomavirus E5 oncoproteins bind the A4 endoplasmic reticulum protein to regulate proliferative ability upon differentiation

Abstract Human papillomaviruses (HPV) infect stratified epithelia and link their life cycles to epithelial differentiation. The HPV E5 protein plays a role in the productive phase of the HPV life cycle but its mechanism of action is still unclear. We identify a new binding partner of E5, A4, using a...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2014-03, Vol.452, p.223-230
Main Authors: Kotnik Halavaty, Katarina, Regan, Jennifer, Mehta, Kavi, Laimins, Laimonis
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Amplification
Bap31
Cell Differentiation
CELL PROLIFERATION
COMPLEXES
Differentiation
Endoplasm
ENDOPLASMIC RETICULUM
Endoplasmic Reticulum - metabolism
Endoplasmic Reticulum - virology
EPITHELIUM
Human papillomavirus
Human papillomavirus 16 - genetics
Human papillomavirus 16 - metabolism
Human papillomavirus 31 - genetics
Human papillomavirus 31 - metabolism
HUMAN POPULATIONS
Humans
Infectious Disease
Keratinocyte
Keratinocytes - cytology
Keratinocytes - metabolism
Keratinocytes - virology
LAYERS
LIFE CYCLE
MARVEL Domain-Containing Proteins
MEMBRANES
Oncogene Proteins, Viral - genetics
Oncogene Proteins, Viral - metabolism
Papillomavirus Infections - genetics
Papillomavirus Infections - metabolism
Papillomavirus Infections - physiopathology
Papillomavirus Infections - virology
Protein Binding
PROTEINS
Proteolipids
Two-Hybrid System Techniques
Viral Proteins - genetics
Viral Proteins - metabolism
YEASTS
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Summary:Abstract Human papillomaviruses (HPV) infect stratified epithelia and link their life cycles to epithelial differentiation. The HPV E5 protein plays a role in the productive phase of the HPV life cycle but its mechanism of action is still unclear. We identify a new binding partner of E5, A4, using a membrane-associated yeast-two hybrid system. The A4 protein co-localizes with HPV 31 E5 in perinuclear regions and forms complexes with E5 and Bap31. In normal keratinocytes, A4 is found primarily in basal cells while in HPV positive cells high levels of A4 are seen in both undifferentiated and differentiated cells. Reduction of A4 expression by shRNAs, enhanced HPV genome amplification and increased cell proliferation ability following differentiation but this was not seen in cells lacking E5. Our studies suggest that the A4 protein is an important E5 binding partner that plays a role in regulating cell proliferation ability upon differentiation.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2014.01.013