title: 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 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.
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kotnik Halavaty
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Regan
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
authors.forename: Kavi
authors.initials: K
authors.lastname: Mehta
authors.affiliation: Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA. Electronic address: l-laimins@northwestern.edu.
authors.forename: Laimonis
authors.initials: L
authors.lastname: Laimins
mesh_terms: D002454:Cell Differentiation; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000821:virology; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D058952:Human papillomavirus 31 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D062792:MARVEL Domain-Containing Proteins; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D011485:Protein Binding; D011510:Proteolipids; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D062792:MARVEL Domain-Containing Proteins; D009856:Oncogene Proteins, Viral; D011510:Proteolipids; D014764:Viral Proteins; C472239:E5 protein, Human papillomavirus type 31; C094765:PLP2 protein, human; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins
keywords: A4; Amplification; Bap31; Differentiation; E5; Endoplasm; Keratinocyte