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Viral Activation of MK2-hsp27-p115RhoGEF-RhoA Signaling Axis Causes Cytoskeletal Rearrangements, P-body Disruption and ARE-mRNA Stabilization


We have only scratched the surface in understanding how viruses control host gene expression. Several viruses disrupt important sites of post-transcriptional control of gene expression known as processing bodies (PBs), but underlying regulatory mechanisms and biological relevance remain poorly understood in most cases. Our study shows that the Kaposin B (KapB) protein of Kaposi's sarcoma (KS)-associated herpesvirus, known to block the degradation of a class of labile host mRNAs, does so by constitutively activating a signaling axis involving MK2, hsp27, p115RhoGEF and RhoA, thereby dispersing PBs. Thus, PB disruption may support the secretion of host pro-inflammatory cytokines and angiogenic factors that underlies KS tumor formation. Furthermore, by activating RhoA, KapB also causes cytoskeletal rearrangements, accelerated cell migration and angiogenesis in an endothelial cell model. Our findings position KapB as a key contributor to viral reprogramming of endothelial cells.


Vyšlo v časopise: Viral Activation of MK2-hsp27-p115RhoGEF-RhoA Signaling Axis Causes Cytoskeletal Rearrangements, P-body Disruption and ARE-mRNA Stabilization. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004597
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004597

Souhrn

We have only scratched the surface in understanding how viruses control host gene expression. Several viruses disrupt important sites of post-transcriptional control of gene expression known as processing bodies (PBs), but underlying regulatory mechanisms and biological relevance remain poorly understood in most cases. Our study shows that the Kaposin B (KapB) protein of Kaposi's sarcoma (KS)-associated herpesvirus, known to block the degradation of a class of labile host mRNAs, does so by constitutively activating a signaling axis involving MK2, hsp27, p115RhoGEF and RhoA, thereby dispersing PBs. Thus, PB disruption may support the secretion of host pro-inflammatory cytokines and angiogenic factors that underlies KS tumor formation. Furthermore, by activating RhoA, KapB also causes cytoskeletal rearrangements, accelerated cell migration and angiogenesis in an endothelial cell model. Our findings position KapB as a key contributor to viral reprogramming of endothelial cells.


Zdroje

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