2004
DOI: 10.1073/pnas.0401897101
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Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria

Abstract: We report that the cytomegalovirus-encoded cell death suppressor vMIA binds Bax and prevents Bax-mediated mitochondrial membrane permeabilization by sequestering Bax at mitochondria in the form of a vMIA–Bax complex. vMIA mutants with a defective mitochondria-targeting domain retain their Bax-binding function but not their ability to suppress mitochondrial membrane permeabilization or cell death. vMIA does not seem to either specifically associate with Bak or suppress Bak-mediated mitochondrial membrane permea… Show more

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Cited by 181 publications
(251 citation statements)
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References 48 publications
(43 reference statements)
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“…When the bridges transiently form between the MAM and mitochondria, UL37 proteins could traffic into the mitochondrial outer membrane, where they have antiapoptotic activity. Its topology and anchoring to membranes enables pUL37x1 to preferentially interact with the membrane-bound proapoptotic Bax protein, inducing its oligomerization and leading to its functional neutralization (5,32). Nonetheless, the finding that multiple HCMV UL37 proteins traffic into the MAM, whereas only a subset of these is specifically committed into mitochondrial importation, shows that MAM localization is insufficient to commit UL37 proteins into mitochondrial importation.…”
Section: Vol 82 2008 Hcmv Pul37x1 Traffics Through the Mam 2721mentioning
confidence: 55%
See 1 more Smart Citation
“…When the bridges transiently form between the MAM and mitochondria, UL37 proteins could traffic into the mitochondrial outer membrane, where they have antiapoptotic activity. Its topology and anchoring to membranes enables pUL37x1 to preferentially interact with the membrane-bound proapoptotic Bax protein, inducing its oligomerization and leading to its functional neutralization (5,32). Nonetheless, the finding that multiple HCMV UL37 proteins traffic into the MAM, whereas only a subset of these is specifically committed into mitochondrial importation, shows that MAM localization is insufficient to commit UL37 proteins into mitochondrial importation.…”
Section: Vol 82 2008 Hcmv Pul37x1 Traffics Through the Mam 2721mentioning
confidence: 55%
“…These sequences include a strongly hydrophobic leader (aa 1 to 22) and a juxtaposed basic domain (aa 23 to 34), which jointly serve as a bipartite signal to target UL37 proteins to the ER and mitochondria (25,27). This NH 2 -terminal targeting domain constitutes the first UL37x1 antiapoptotic domain, which when combined with a downstream domain (aa 118 to 147) are sufficient to confer its antiapoptotic activity (5,18,19,28,32,34,45). Between the UL37x1 antiapoptotic domains lies an acidic domain (aa 81 to 108), which plays a role in the transactivation of HCMV early gene promoters, whose products are needed for its oriLyt replication (13,31,52).…”
mentioning
confidence: 99%
“…However, the antiapoptotic proteins expressed by human cytomegalovirus vMIA and that expressed by myxoma virus M11L sequester Bax 31 and Bak, 32 respectively. To test this hypothesis for F1L-function, we initially assessed the capacity of purified recombinant F1L expressed in Escherichia coli to bind Bcl-2 homology domain (BH3 domain) peptides since these regions mediate the killing activity of the proapoptotic BH3-only proteins as well as Bax/Bak.…”
Section: Analysis Of Apoptosis Induction By Mva-df1lmentioning
confidence: 99%
“…Conversely, PACS-1 can bind de-phosphorylated Bid and block translocation to mitochondria, suggesting a mechanism to impede the apoptotic program. In HCMV-infected cells, vMIA traps PACS-2 and Bax on mitochondria, suppressing Bid recruitment and MOMP (Arnoult et al, 2004;Salka et al, 2017; Fig. 5A,C).…”
Section: Discussionmentioning
confidence: 99%
“…Not surprisingly, herpesviruses also exploit the ability of PACS-2 to traffic proteins to mitochondria. The HCMV protein viral inhibitor of apoptosis (vMIA) prevents cell death by trapping proapoptotic Bax on mitochondria (Arnoult et al, 2004). vMIA interacts with PACS-2 but not PACS-1 (our unpublished data), and the vMIA- PACS-2 interaction is required for efficient translocation of vMIA to mitochondria (Salka et al, 2017).…”
Section: Introductionmentioning
confidence: 99%