title: Regulation of Na(+)-coupled glucose carrier SGLT1 by human papillomavirus 18 E6 protein.
abstract: Tumor cells utilize preferably glucose for energy production. They accomplish cellular glucose uptake in part through Na(+)-coupled glucose transport mediated by SGLT1 (SLC5A1). This study explored the possibility that the human papillomavirus 18 E6 protein HPV18 E6 (E6) participates in the stimulation of SGLT1 activity. E6 is one of the two major oncoproteins of high-risk human papillomaviruses, which are the causative agent for cervical carcinoma. According to Western blotting, SGLT1 is expressed in the HPV18-positive cervical carcinoma cell line HeLa. To explore whether E6 affects SGLT1 activity, SGLT1 was expressed in Xenopus oocytes with and without E6 and electrogenic glucose transport determined by dual electrode voltage clamp. In SGLT1-expressing oocytes, but not in oocytes injected with water or expressing E6 alone, glucose triggered a current (I(g)). I(g) was significantly increased by coexpression of E6 but not by coexpression of E2. According to chemiluminescence and confocal microscopy, coexpression of E6 significantly increased the SGLT1 protein abundance in the cell membrane. The decay of I(g) following inhibition of carrier insertion by Brefeldine A (5 μM) was not significantly affected E6 coexpression. Accrodingly, E6 was not effective by increasing carrier protein stability in the membrane. In conclusion, HPV18 E6 oncoprotein participates in the upregulation of SGLT1.
authors.affiliation: Institute for Medical Virology and Epidemiology of Viral Diseases, Division of Experimental Virology, University of Tuebingen, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Leiprecht
authors.forename: Carlos
authors.initials: C
authors.lastname: Munoz
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Gulab
authors.initials: G
authors.lastname: Siraskar
authors.forename: Mentor
authors.initials: M
authors.lastname: Sopjani
authors.forename: Michael
authors.initials: M
authors.lastname: Föller
authors.forename: Frank
authors.initials: F
authors.lastname: Stubenrauch
authors.forename: Thomas
authors.initials: T
authors.lastname: Iftner
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism* / Q000821:virology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells; D052161:Human papillomavirus 18 / Q000378:metabolism*; D006801:Humans; D008163:Luminescent Measurements; D018613:Microscopy, Confocal; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D009865:Oocytes; D051269:Sodium-Glucose Transporter 1 / Q000819:agonists / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology; D014981:Xenopus
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D020126:Brefeldin A; D005947:Glucose