Exploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release

Votteler, Jörg; Iavnilovitch, Elena; Fingrut, Orit; Shemesh, Vivian; Taglicht, Daniel; Erez, Omri; Sörgel, Stefan; Walther, Torsten; Bannert, Norbert; Schubert, Ulrich S.; Reiss, Yuval

doi:10.1186/1471-2091-10-12

Cited by 22 publications

(18 citation statements)

References 45 publications

(67 reference statements)

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“…It has been recently reported that in overexpressing human cell lines, Alix interacts with and is ubiquitinated by the onechain ligases POSH and Nedd4-1 during the process of virus budding (25,26). It is noteworthy that the interaction of Alix with these two ligases was detected only in the presence of detergents.…”

Section: Discussionmentioning

confidence: 96%

“…It is noteworthy that among the proteins known to interact directly or indirectly with Alix are components of the ubiquitin pathway, including the deubiquitinating enzyme Doa4 and the E3 ubiquitin ligases Cbl, POSH (plenty of Src homology 3), and Nedd4-1 (25)(26)(27)(28). The latter two ligases have been shown to ubiquitinate and cooperate with Alix during the process of HIV-1 release.…”

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confidence: 99%

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Alix Protein Is Substrate of Ozz-E3 Ligase and Modulates Actin Remodeling in Skeletal Muscle

Bongiovanni

Romancino

Campos

et al. 2012

Journal of Biological Chemistry

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Background: Alix participates in fundamental cellular processes, but how it is regulated remains unknown. Results: Alix is ubiquitinated by the Ozz-E3 ligase and participates in actin cytoskeleton remodeling, filopodia formation, and myoblast migration. Conclusion: Ozz influences Alix conformation and in turn the extent of ubiquitination in Alix. Significance: Ozz-E3 ligase regulates Alix concentration at sites where the actin cytoskeleton undergoes remodeling.

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Alix Protein Is Substrate of Ozz-E3 Ligase and Modulates Actin Remodeling in Skeletal Muscle

Bongiovanni

Romancino

Campos

et al. 2012

Journal of Biological Chemistry

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“…The expression plasmid containing hemagglutinin (HA)-tagged Ub (pHA-Ub) was obtained from H.-G. Kräusslich and is described elsewhere (28). Construction of pCMV-Flag-ALIX is described elsewhere (36).…”

Section: Plasmid Constructs and Small Interfering Rnamentioning

confidence: 99%

The PTAP Sequence within the p6 Domain of Human Immunodeficiency Virus Type 1 Gag Regulates Its Ubiquitination and MHC Class I Antigen Presentation

Hahn

Setz

Wild

et al. 2011

The Journal of Immunology

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Endogenous peptides presented by MHC class I (MHC-I) molecules are mostly derived from de novo synthesized, erroneous proteins, so-called defective ribosomal products (DRiPs), which are rapidly degraded via the ubiquitin–proteasome pathway. We have previously shown that the HIV-1 Gag protein represents a bona fide substrate for the DRiP pathway and that the amount of Gag-DRiPs can be enhanced by the introduction of an N-end rule degradation signal, leading to increased MHC-I presentation and immunogenicity of Gag. Based on these findings, we sought to identify a naturally occurring sequence motif within Gag that regulates its entry into the DRiP pathway. As the PTAP late assembly domain motif in the C-terminal p6 domain of Gag has been shown to negatively regulate the ubiquitination of Gag, we analyzed the correlation between ubiquitination and MHC-I presentation of PTAP-deficient Gag. Intriguingly, mutation of PTAP not only reduces the release of virus-like particles, but also increases ubiquitination of Gag and, consistently, enhances MHC-I presentation of a Gag-derived epitope. Although the half-life of the PTAP mutant was only mildly reduced, the entry into the DRiP pathway was significantly increased, as demonstrated by short-term pulse-chase analyses under proteasome inhibition. Collectively, these results indicate that, besides driving virus release, the PTAP motif regulates the entry of Gag into the DRiP pathway and, thus, into the MHC-I pathway. Although there are no naturally occurring PTAP mutants of HIV-1, mutations of PTAP might enhance the immunogenicity of Gag and, thus, be considered for the improvement of vaccine development.

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“…Indeed, several cellular factors involved in endosomal sorting pathways have been identified to play some roles in HIV-1 Gag trafficking and particle assembly. These factors include adaptor protein complexes (16 -18), GGA (Golgi-localized ␥-ear-containing, Arf binding) and Arf (ADP-ribosylation factor) proteins (19), annexin 2 (20), ubiquitin E3 ligase POSH (plenty of SH3s) (21,22), and SOCS1 (the suppressor of cytokine signaling 1) (23).…”

mentioning

confidence: 99%

Filamin A Protein Interacts with Human Immunodeficiency Virus Type 1 Gag Protein and Contributes to Productive Particle Assembly

Cooper¹,

Liu²,

Woodruff

et al. 2011

Journal of Biological Chemistry

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HIV-1 Gag precursor directs virus particle assembly and release. In a search for Gag-interacting proteins that are involved in late stages of the HIV-1 replication cycle, we performed yeast two-hybrid screening against a human cDNA library and identified the non-muscle actin filament cross-linking protein filamin A as a novel Gag binding partner. The 280-kDa filamin A regulates cortical actin network dynamics and participates in the anchoring of membrane proteins to the actin cytoskeleton. Recent studies have shown that filamin A facilitates HIV-1 cell-to-cell transmission by binding to HIV receptors and coreceptors and regulating their clustering on the target cell surface. Here we report a novel role for filamin A in HIV-1 Gag intracellular trafficking. We demonstrate that filamin A interacts with the capsid domain of HIV-1 Gag and that this interaction is involved in particle release in a productive manner. Disruption of this interaction eliminated Gag localization at the plasma membrane and induced Gag accumulation within internal compartments. Moreover, blocking clathrin-dependent endocytic pathways did not relieve the restriction to particle release induced by filamin A depletion. These results suggest that filamin A is involved in the distinct step of the Gag trafficking pathway. The discovery of the Gag-filamin A interaction may provide a new therapeutic target for the treatment of HIV infection.

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Exploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release

Cited by 22 publications

References 45 publications

Alix Protein Is Substrate of Ozz-E3 Ligase and Modulates Actin Remodeling in Skeletal Muscle

Alix Protein Is Substrate of Ozz-E3 Ligase and Modulates Actin Remodeling in Skeletal Muscle

The PTAP Sequence within the p6 Domain of Human Immunodeficiency Virus Type 1 Gag Regulates Its Ubiquitination and MHC Class I Antigen Presentation

Filamin A Protein Interacts with Human Immunodeficiency Virus Type 1 Gag Protein and Contributes to Productive Particle Assembly

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