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2009-04-24Zeitschriftenartikel DOI: 10.1186/1471-2091-10-12
Exploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release
dc.contributor.authorVotteler, Jörg
dc.contributor.authorIavnilovitch, Elena
dc.contributor.authorFingrut, Orit
dc.contributor.authorShemesh, Vivian
dc.contributor.authorTaglicht, Daniel
dc.contributor.authorErez, Omri
dc.contributor.authorSörgel, Stefan
dc.contributor.authorWalther, Torsten
dc.contributor.authorBannert, Norbert
dc.contributor.authorSchubert, Ulrich
dc.contributor.authorReiss, Yuval
dc.date.accessioned2018-05-07T13:22:29Z
dc.date.available2018-05-07T13:22:29Z
dc.date.created2009-11-09
dc.date.issued2009-04-24none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/regN22ZePO96/PDF/28syM6KOfJ0Bw.pdf
dc.identifier.urihttp://edoc.rki.de/176904/476
dc.description.abstractBackground: The ALG2-interacting protein X (ALIX)/AIP1 is an adaptor protein with multiple functions in intracellular protein trafficking that plays a central role in the biogenesis of enveloped viruses. The ubiquitin E3-ligase POSH (plenty of SH3) augments HIV-1 egress by facilitating the transport of Gag to the cell membrane. Recently, it was reported, that POSH interacts with ALIX and thereby enhances ALIX mediated phenotypes in Drosophila. Results: In this study we identified ALIX as a POSH ubiquitination substrate in human cells: POSH induces the ubiquitination of ALIX that is modified on several lysine residues in vivo and in vitro. This ubiquitination does not destabilize ALIX, suggesting a regulatory function. As it is well established that ALIX rescues virus release of L-domain mutant HIV-1, HIV-1ΔPTAP, we demonstrated that wild type POSH, but not an ubiquitination inactive RING finger mutant (POSHV14A), substantially enhances ALIX-mediated release of infectious virions derived from HIV-1ΔPTAP L-domain mutant (YPXnL-dependent HIV-1). In further agreement with the idea of a cooperative function of POSH and ALIX, mutating the YPXnL-ALIX binding site in Gag completely abrogated augmentation of virus release by overexpression of POSH. However, the effect of the POSH-mediated ubiquitination appears to be auxiliary, but not necessary, as silencing of POSH by RNAi does not disturb ALIX-augmentation of virus release. Conclusion: Thus, the cumulative results identified ALIX as an ubiquitination substrate of POSH and indicate that POSH and ALIX cooperate to facilitate efficient virus release. However, while ALIX is obligatory for the release of YPXnL-dependent HIV-1, POSH, albeit rate-limiting, may be functionally interchangeable.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut
dc.subjectWesterneng
dc.subjectCell Lineeng
dc.subjectHumanseng
dc.subjectVirus Replicationeng
dc.subjectMutationeng
dc.subjectBlottingeng
dc.subjectHIV-1/geneticseng
dc.subjectImmunoprecipitationeng
dc.subjectBinding Sites/geneticseng
dc.subjectCalcium-Binding Proteins/geneticseng
dc.subjectCalcium-Binding Proteins/metabolismeng
dc.subjectCell Cycle Proteins/geneticseng
dc.subjectCell Cycle Proteins/metabolismeng
dc.subjectHIV-1/physiologyeng
dc.subjectHela Cellseng
dc.subjectProtein Bindingeng
dc.subjectRecombinant Proteins/metabolismeng
dc.subjectSubstrate Specificityeng
dc.subjectTransfectioneng
dc.subjectUbiquitin-Protein Ligases/geneticseng
dc.subjectUbiquitin-Protein Ligases/metabolismeng
dc.subjectUbiquitinationeng
dc.subjectVirus Assemblyeng
dc.subject.ddc610 Medizin
dc.titleExploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-1002813
dc.identifier.doi10.1186/1471-2091-10-12
dc.identifier.doihttp://dx.doi.org/10.25646/401
local.edoc.container-titleBMC Biochemistry
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.biomedcentral.com/1471-2091/10/12
local.edoc.container-publisher-nameBioMed Central
local.edoc.container-volume10
local.edoc.container-issue12
local.edoc.container-year2009

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