2. Academic Validation
  3. The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production

The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production

  • Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1478-83. doi: 10.1073/pnas.0408717102.
Iris Alroy 1,  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
Affiliations

Affiliation

  • 1 Proteologics Ltd., 2 Holzman Street, Rehovot Science Park, Rehovot 76124, Israel.
PMID: 15659549 DOI: 10.1073/pnas.0408717102
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.

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