This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Disbrow, G. L.
Right arrow Articles by Schlegel, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Disbrow, G. L.
Right arrow Articles by Schlegel, R.

 Previous Article  |  Next Article 

Journal of Virology, May 2005, p. 5839-5846, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5839-5846.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Endoplasmic Reticulum-Localized Human Papillomavirus Type 16 E5 Protein Alters Endosomal pH but Not trans-Golgi pH

Gary L. Disbrow,1 John A. Hanover,2 and Richard Schlegel1*

Department of Pathology, Georgetown University Medical School, Washington, D.C. 20057,1 Laboratory of Cell Biochemistry and Biology, NIDDK, NIH, Bethesda, Maryland2

Received 23 September 2004/ Accepted 23 November 2004

The human papillomavirus type 16 (HPV-16) E5 protein is a small, hydrophobic polypeptide that is expressed in virus-infected keratinocytes and alters receptor signaling pathways, apoptotic responses, and endosomal pH. Despite its ability to inhibit endosomal acidification, the HPV-16 E5 protein is found predominantly in the endoplasmic reticulum (ER), suggesting that its effect may be indirect and perhaps global. To determine whether E5 alters the pHs of additional intracellular compartments, we transduced human keratinocytes with a codon-optimized E5 vector and then quantified endosomal and trans-Golgi pHs using sensitive, compartment-specific, ratiometric pHluorin constructs. E5 protein increased endosomal pH from 5.9 to 6.9 but did not affect the normal trans-Golgi pH of 6.3. Confirming the lack of alteration in trans-Golgi pH, we observed no alterations in the acidification-dependent processing of the proH3 protein. C-terminal deletions of E5, which retained normal expression and localization in the ER, were defective for endosomal alkalization. Thus, E5 does not uniformly alkalinize intracellular compartments, and its C-terminal 10 amino acids appear to mediate interactions with critical ER targets that modulate proton pump function and/or localization.

* Corresponding author. Mailing address: Department of Pathology, Georgetown University Medical School, Basic Science Building, Room 113, 3900 Reservoir Rd., NW, Washington, DC 20057. Phone: (202) 687-7733. Fax: (202) 687-2933. E-mail: schleger{at}georgetown.edu.

Journal of Virology, May 2005, p. 5839-5846, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5839-5846.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Regan, J. A., Laimins, L. A. (2008). Bap31 Is a Novel Target of the Human Papillomavirus E5 Protein. J. Virol. 82: 10042-10051 [Abstract] [Full Text]  
  • Krawczyk, E., Suprynowicz, F. A., Liu, X., Dai, Y., Hartmann, D. P., Hanover, J., Schlegel, R. (2008). Koilocytosis: A Cooperative Interaction between the Human Papillomavirus E5 and E6 Oncoproteins. Am. J. Pathol. 173: 682-688 [Abstract] [Full Text]  
  • Genther Williams, S. M., Disbrow, G. L., Schlegel, R., Lee, D., Threadgill, D. W., Lambert, P. F. (2005). Requirement of Epidermal Growth Factor Receptor for Hyperplasia Induced by E5, a High-Risk Human Papillomavirus Oncogene. Cancer Res. 65: 6534-6542 [Abstract] [Full Text]  
  • McCance, D. J. (2005). Human Papillomaviruses and Cell Signaling. Sci Signal 2005: pe29-pe29 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»