Abstract
Recent studies have demonstrated nuclear export by papillomavirus E1 proteins, but the requisite export sequence(s) for bovine papillomavirus (BPV) E1 were not defined. In this report we identify three functional nuclear export sequences (NES) present in BPV E1, with NES2 being the strongest in reporter assays. Nuclear localization of BPV1 E1 was modulated by over- or under-expression of CRM1, the major cellular exportin, and export was strongly reduced by the CRM1 inhibitor, Leptomycin B, indicating that E1 export occurs primarily through a CRM1-dependent process. Consistent with the in vivo functional results, E1 bound CRM1 in an in vitro pull-down assay. In addition, sumoylated E1 bound CRM1 more effectively than unmodified E1, suggesting that E1 export may be regulated by SUMO modification. Lastly, an E1 NES2 mutant accumulated in the nucleus to a greater extent than wild-type E1, yet was defective for viral origin replication in vivo. However, NES2 exhibited no intrinsic replication defect in an in vitro replication assay, implying that nucleocytoplasmic shuttling may be required to maintain E1 in a replication competent state.
References
Feb 17, 1997·The EMBO Journal·M FornerodG Grosveld
Feb 1, 1997·Chemistry & Biology·B WolffY Wang
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·D C LoveJ A Hanover
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·N KudoS Horinouchi
Mar 31, 2000·Experimental Cell Research·B R Henderson, A Eleftheriou
Jun 29, 2000·The Journal of Biological Chemistry·D Rangasamy, V G Wilson
Jun 30, 2000·Virology·A A AminJ Archambault
Aug 19, 2000·Molecular Cell·E J EnemarkL Joshua-Tor
Sep 27, 2000·The Journal of Biological Chemistry·D RangasamyV G Wilson
Jan 17, 2002·Cell·Andrea PichlerFrauke Melchior
Mar 13, 2002·The EMBO Journal·Eric J EnemarkLeemor Joshua-Tor
Mar 16, 2002·The Journal of Biological Chemistry·Jun Hang, Mary Dasso
Jun 14, 2002·Developmental Cell·Alex SobkoRichard A Firtel
Aug 23, 2002·Molecular and Cellular Biology·Hong ZhangMichael J Matunis
Jan 17, 2003·Molecular Biology of the Cell·Michael K ConnorJoyce M Slingerland
Mar 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lauren D WoodScott W Hiebert
Apr 15, 2003·Journal of Virology·S TitoloJ Archambault
Apr 15, 2004·Molecular and Cellular Biology·Maria T Vassileva, Michael J Matunis
Aug 27, 2004·The EMBO Journal·Dieuwke EngelsmaMaarten Fornerod
Nov 27, 2004·Journal of Virology·Wentao DengLouise T Chow
Dec 8, 2004·Virology·Germán Rosas-AcostaVan G Wilson
Mar 9, 2005·Trends in Cell Biology·Ulrike Kutay, Stephan Güttinger
Oct 13, 2006·Journal of Virology·Chiung-Yueh HsuCatherine Bonne-Andrea
Dec 29, 2006·Journal of Virology·Xue-Lin BianVan G Wilson
Apr 13, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kathrin KindsmüllerThomas Dobner
Citations
Sep 11, 2008·The Journal of Biological Chemistry·James X DuVincent W Yang
Sep 26, 2014·Viruses·Van G Wilson
Oct 16, 2015·Archives of Virology·Michael R Lentz, Tess Shideler
Dec 23, 2011·Biology of the Cell·Yao E WangBenhur Lee
Mar 28, 2012·The Biochemical Journal·Olga PekarMia Horowitz
Sep 14, 2013·Virology·Monika BergvallJacques Archambault
May 3, 2011·Biochimica Et Biophysica Acta·Alex J Fulcher, David A Jans
Oct 20, 2009·Virology·Amélie Fradet-TurcotteJacques Archambault