Viral Inhibition of BAK Promotes Murine Cytomegalovirus Dissemination to Salivary Glands

Handke, Wiebke; Luig, Christina; Popović, Branka; Krmpotić, Astrid; Jonjić, Stipan; Brune, Wolfram

doi:10.1128/jvi.02657-12

Cited by 28 publications

(21 citation statements)

References 31 publications

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“…The anti-apoptotic functions of viral proteins rely on blocking BAK or BAX activation by direct interaction with these proteins [72, 73]. Although most inhibitors follow canonical BH3–into–BC groove inhibitory mechanisms and can inhibit BH3 regions of BCL-2 family activators and effectors [74], some viral inhibitors engage different sites on the effectors, thereby preventing their activation.…”

Section: Non-canonical Bc Groove Mechanismsmentioning

confidence: 99%

Many players in BCL-2 family affairs

Moldoveanu

Follis

Kriwacki

et al. 2014

Trends in Biochemical Sciences

369

299

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During apoptotic cell death, cellular stress signals converge at the mitochondria to induce mitochondrial outer membrane permeabilization (MOMP) through BCL-2 family proteins and their effectors. BCL-2 proteins function through protein-protein interactions, the mechanisms and structural aspects of which are only just being uncovered. Recently, the elucidation of the dynamic features underlying their function has highlighted their structural plasticity and the consequent complex thermodynamic landscape governing their protein-protein interactions. These studies show that canonical interactions involve a conserved, hydrophobic groove, whereas noncanonical interactions function allosterically outside the groove. Here, we review the latest structural advances in understanding the interactions and functions of mammalian BCL-2 family members and discuss new opportunities to modulate these proteins in health and disease.

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Section: Non-canonical Bc Groove Mechanismsmentioning

confidence: 99%

Many players in BCL-2 family affairs

Moldoveanu

Follis

Kriwacki

et al. 2014

Trends in Biochemical Sciences

369

299

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“…Therefore, virus, in turn, can activate signalling pathways to prevent host cellular death [7]. The anti-apoptotic cellular machinery includes several proteins, among which the BAG family molecular chaperone regulator 3 (BAG3).…”

Section: Introductionmentioning

confidence: 99%

BAG3 protects Bovine Papillomavirus type 1-transformed equine fibroblasts against pro-death signals

Cotugno

Gallotta

d’Avenia

et al. 2013

Vet Res

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In human cancer cells, BAG3 protein is known to sustain cell survival. Here, for the first time, we demonstrate the expression of BAG3 protein both in equine sarcoids in vivo and in EqS04b cells, a sarcoid-derived fully transformed cell line harbouring bovine papilloma virus (BPV)-1 genome. Evidence of a possible involvement of BAG3 in equine sarcoid carcinogenesis was obtained by immunohistochemistry analysis of tumour samples. We found that most tumour samples stained positive for BAG3, even though to a different grade, while normal dermal fibroblasts from healthy horses displayed very weak staining pattern for BAG3 expression. By siRNA technology, we demonstrate in EqS04b the role of BAG3 in counteracting basal as well as chemical-triggered pro-death signals. BAG3 down-modulation was indeed shown to promote cell death and cell cycle arrest in G0/G1. In addition, we found that BAG3 silencing sensitized EqS04b cells to phenethylisothiocyanate (PEITC), a promising cancer chemopreventive/chemotherapeutic agent present in edible cruciferous vegetables. Notably, such a pro-survival role of BAG3 was less marked in E. Derm cells, an equine BPV-negative fibroblast cell line taken as a normal counterpart. Altogether our findings might suggest a mutual cooperation between BAG3 and viral oncoproteins to sustain cell survival.

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“…This is promising if the viral protein only targets one host protein (e.g. [16,57]). In the present case, such a genetic rescue is unlikely to work as m139 interacts with at least two host proteins, DDX3 and UBR5.…”

Section: Discussionmentioning

confidence: 99%

Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication

Puhach

Ostermann

Frascaroli

et al. 2020

Preprint

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1Cytomegaloviruses (CMV) infect many different cell types and tissues in their respective hosts. 2 Monocytes and macrophages play an important role in CMV dissemination from the site of UBR5, m139 ensures efficient viral replication in endothelial cells. Importantly, we identify 33 m139 as a new viral DDX3 inhibitor, which curtails the production of interferon in 34 macrophages. 35 36 157 to nuclear replication compartments (Figures S1). These finding suggested that the viral m139 158 and E1 proteins interact indirectly or through a weak interaction. 159 7

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Viral Inhibition of BAK Promotes Murine Cytomegalovirus Dissemination to Salivary Glands

Cited by 28 publications

References 31 publications

Many players in BCL-2 family affairs

Many players in BCL-2 family affairs

BAG3 protects Bovine Papillomavirus type 1-transformed equine fibroblasts against pro-death signals

Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication

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