[Proteologic -- HIV target: POSH (human ubiquitin-protein ligase)]
>>Published online before print January 19, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0408717102
The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production
( protein sorting/trafficking | ubiquitin conjugation | ubiquitin ligase | HIV assembly | HIV secretion )
Iris Alroy *, 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 *, and Yuval Reiss *¶
*Proteologics Ltd., 2 Holzman Street, Rehovot Science Park, Rehovot 76124, Israel; and Heinrich-Pette Institute, Hamburg D-20251, Germany
Communicated by Avram Hershko, Technion Israel Institute of Technology, Technion City, Haifa, Israel, December 12, 2004 (received for review July 6, 2004)
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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