| Literature DB >> 15659549 |
Iris Alroy1, Shmuel Tuvia, Tsvika Greener, Daphna Gordon, Haim M Barr, Daniel Taglicht, Revital Mandil-Levin, Danny Ben-Avraham, Dalit Konforty, Anat Nir, Orit Levius, Vivian Bicoviski, Mally Dori, Shenhav Cohen, Liora Yaar, Omri Erez, Oshrat Propheta-Meiran, Mordechai Koskas, Elanite Caspi-Bachar, Iris Alchanati, Alin Sela-Brown, Haim Moskowitz, Uwe Tessmer, Ulrich Schubert, Yuval Reiss.
Abstract
HIV type 1 (HIV-1) was shown to assemble either at the plasma membrane or in the membrane of late endosomes. Now, we report an essential role for human ubiquitin ligase POSH (Plenty of SH3s; hPOSH), a trans-Golgi network-associated protein, in the targeting of HIV-1 to the plasma membrane. Small inhibitory RNA-mediated silencing of hPOSH ablates virus secretion and Gag plasma membrane localization. Reintroduction of native, but not a RING finger mutant, hPOSH restores virus release and Gag plasma membrane localization in hPOSH-depleted cells. Furthermore, expression of the RING finger mutant hPOSH inhibits virus release and induces accumulation of intracellular Gag in normal cells. Together, our results identify a previously undescribed step in HIV biogenesis and suggest a direct function for hPOSH-mediated ubiquitination in protein sorting at the trans-Golgi network. Consequently, hPOSH may be a useful host target for therapeutic intervention.Entities:
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Year: 2005 PMID： 15659549 PMCID： PMC545085 DOI： 10.1073/pnas.0408717102
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205