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 Jäger, S.
Right arrow Articles by Kräusslich, H.-G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jäger, S.
Right arrow Articles by Kräusslich, H.-G.

 Previous Article  |  Next Article 

Journal of Virology, September 2007, p. 9193-9201, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00044-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Ubiquitination of Human Immunodeficiency Virus Type 1 Gag Is Highly Dependent on Gag Membrane Association{triangledown}

Stefanie Jäger, Eva Gottwein,{dagger} and Hans-Georg Kräusslich*

Abteilung Virologie, Universitätsklinikum Heidelberg, D-69120 Heidelberg, Germany

Received 8 January 2007/ Accepted 16 June 2007

Ubiquitin is important for the release of human immunodeficiency virus 1 (HIV-1) and several other retroviruses. All major domains of the HIV-1 Gag protein are monoubiquitinated, but the modifying machinery and the function of HIV-1 Gag ubiquitination remain unclear. Here, we show that the induction of a late budding arrest by mutation of the HIV-1 PTAP motif or by specific inhibition of selected ESCRT components leads to an increase of Gag-ubiquitin conjugates in cells, which coincides with an accumulation of detergent-insoluble, multimerized Gag at the plasma membrane. Membrane flotation experiments revealed that ubiquitinated Gag is highly enriched in membrane-bound fractions. Based on these findings, we propose that a blocking of virus release results in increased Gag ubiquitination as a consequence of its prolonged membrane association. Consistent with this, ubiquitination of a membrane-binding-defective (G2A)Gag mutant was dramatically reduced and the ubiquitination levels of truncated Gag proteins correlated with their abilities to bind to membranes. We therefore propose that membrane association and multimerization of HIV-1 Gag proteins, rather than a specific motif within Gag, trigger recognition by the cellular ubiquitination machinery.

* Corresponding author. Mailing address: Abteilung Virologie, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany. Phone: 49-6221-565002. Fax: 49-6221-565003. E-mail: Hans-Georg.Kraeusslich{at}med.uni-heidelberg.de

{triangledown} Published ahead of print on 3 July 2007.

{dagger} Present address: Department of Microbiology and Genetics, Box 3025, Duke University Medical Center, Durham, NC 27710.

Journal of Virology, September 2007, p. 9193-9201, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00044-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hogue, I. B., Hoppe, A., Ono, A. (2009). Quantitative Fluorescence Resonance Energy Transfer Microscopy Analysis of the Human Immunodeficiency Virus Type 1 Gag-Gag Interaction: Relative Contributions of the CA and NC Domains and Membrane Binding. J. Virol. 83: 7322-7336 [Abstract] [Full Text]  
  • Liu, Y., Shah, S. V., Xiang, X., Wang, J., Deng, Z.-b., Liu, C., Zhang, L., Wu, J., Edmonds, T., Jambor, C., Kappes, J. C., Zhang, H.-G. (2009). COP9-Associated CSN5 Regulates Exosomal Protein Deubiquitination and Sorting. Am. J. Pathol. 174: 1415-1425 [Abstract] [Full Text]  
  • Goldwich, A., Hahn, S. S. C., Schreiber, S., Meier, S., Kampgen, E., Wagner, R., Lutz, M. B., Schubert, U. (2008). Targeting HIV-1 Gag into the Defective Ribosomal Product Pathway Enhances MHC Class I Antigen Presentation and CD8+ T Cell Activation. J. Immunol. 180: 372-382 [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»