title: YIP1 family member 4 (YIPF4) is a novel cellular binding partner of the papillomavirus E5 proteins.
abstract: E5 proteins are amongst the least understood of the Human Papillomavirus (HPV) encoded gene products. They are small, membrane-integrated proteins known to modulate a number of critical host pathways associated with pathogenesis including growth factor receptor signaling and immune evasion. Their role in the virus life cycle is less clear, indicating a role in the productive stages of the life cycle. However, a mechanism for this is currently lacking. Here we describe the identification of a novel binding partner of E5, YIPF4 using yeast two-hybrid analysis. YIPF4 is also a poorly characterized membrane spanning protein. Mutagenesis studies implicated the transmembrane regions of each protein as important for their interaction. Binding to YIPF4 was found for all E5 proteins tested suggesting that this interaction may mediate a conserved E5 function. In normal human keratinocytes YIPF4 expression was down-regulated upon differentiation and this reduction was partially rescued in cells harbouring HPV. Despite the conserved nature of the interaction with E5, siRNA mediated depletion of YIPF4 failed to impede two well-characterized functions of E5, namely EGFR trafficking or HLA class I presentation. Continued studies of YIPF4 are warranted to determine its role in the PV life cycle.
authors.affiliation: University of Leeds, UK.
authors.forename: Marietta
authors.initials: M
authors.lastname: Müller
authors.affiliation: University of Leeds, UK.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Wasson
authors.affiliation: Division of Pathway Medicine, The University of Edinburgh, UK.
authors.forename: Ramya
authors.initials: R
authors.lastname: Bhatia
authors.affiliation: University of Leeds, UK.
authors.forename: Sally
authors.initials: S
authors.lastname: Boxall
authors.affiliation: Department of Pathology, Southern General Hospital, Glasgow, Scotland, UK.
authors.forename: David
authors.initials: D
authors.lastname: Millan
authors.affiliation: University of Leeds, UK.
authors.forename: Grace Y S
authors.initials: GY
authors.lastname: Goh
authors.affiliation: Division of Pathway Medicine, The University of Edinburgh, UK.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Haas
authors.affiliation: University of Leeds, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Stonehouse
authors.affiliation: University of Leeds, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Macdonald
mesh_terms: D018929:Cell Culture Techniques; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000821:virology; D000086082:Viroporin Proteins
chemical_list: D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins; C052633:E7 protein, Human papillomavirus type 18; C568918:YIPF4 protein, human; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins; C512478:EGFR protein, human