Open AccessThe trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production
Author(s) -
Iris Alroy,
Shmuel Tuvia,
Tsvika Greener,
Daphna Gordon,
Haim 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 ProphetaMeiran,
Mordechai Koskas,
Elanite Caspi-Bachar,
Iris Alchanati,
Alin Sela-Brown,
Haim Moskowitz,
Uwe Tessmer,
Ulrich S. Schubert,
Yuval Reiss
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0408717102
Subject(s) - ubiquitin ligase , microbiology and biotechnology , endosome , brefeldin a , golgi apparatus , biology , ubiquitin , mutant , membrane protein , intracellular , biochemistry , membrane , endoplasmic reticulum , gene
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.