The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production.
Journal - Proceedings of the National Academy of Sciences of the United States of America (United States )
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.
|ISSN : ||0027-8424|
|Mesh Heading : ||Cell Membrane Cloning, Molecular Gene Products, gag Gene Silencing HIV-1 Hela Cells Humans Protein Transport Recombinant Proteins Ubiquitin-Protein Ligases Virus Replication trans-Golgi Network enzymology virology metabolism metabolism genetics|
|Mesh Heading Relevant : ||physiology metabolism physiology enzymology|