title: The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production.
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.
authors.affiliation: Proteologics Ltd., 2 Holzman Street, Rehovot Science Park, Rehovot 76124, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Alroy
authors.forename: Shmuel
authors.initials: S
authors.lastname: Tuvia
authors.forename: Tsvika
authors.initials: T
authors.lastname: Greener
authors.forename: Daphna
authors.initials: D
authors.lastname: Gordon
authors.forename: Haim M
authors.initials: HM
authors.lastname: Barr
authors.forename: Daniel
authors.initials: D
authors.lastname: Taglicht
authors.forename: Revital
authors.initials: R
authors.lastname: Mandil-Levin
authors.forename: Danny
authors.initials: D
authors.lastname: Ben-Avraham
authors.forename: Dalit
authors.initials: D
authors.lastname: Konforty
authors.forename: Anat
authors.initials: A
authors.lastname: Nir
authors.forename: Orit
authors.initials: O
authors.lastname: Levius
authors.forename: Vivian
authors.initials: V
authors.lastname: Bicoviski
authors.forename: Mally
authors.initials: M
authors.lastname: Dori
authors.forename: Shenhav
authors.initials: S
authors.lastname: Cohen
authors.forename: Liora
authors.initials: L
authors.lastname: Yaar
authors.forename: Omri
authors.initials: O
authors.lastname: Erez
authors.forename: Oshrat
authors.initials: O
authors.lastname: Propheta-Meiran
authors.forename: Mordechai
authors.initials: M
authors.lastname: Koskas
authors.forename: Elanite
authors.initials: E
authors.lastname: Caspi-Bachar
authors.forename: Iris
authors.initials: I
authors.lastname: Alchanati
authors.forename: Alin
authors.initials: A
authors.lastname: Sela-Brown
authors.forename: Haim
authors.initials: H
authors.lastname: Moskowitz
authors.forename: Uwe
authors.initials: U
authors.lastname: Tessmer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schubert
authors.forename: Yuval
authors.initials: Y
authors.lastname: Reiss
mesh_terms: D002462:Cell Membrane / Q000201:enzymology / Q000821:virology; D003001:Cloning, Molecular; D015683:Gene Products, gag / Q000378:metabolism; D020868:Gene Silencing; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D011994:Recombinant Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology*; D021601:trans-Golgi Network / Q000201:enzymology*
chemical_list: D015683:Gene Products, gag; D011994:Recombinant Proteins; C498193:SH3RF1 protein, human; D044767:Ubiquitin-Protein Ligases