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Herpesviral G Protein-Coupled Receptors Activate NFAT to Induce Tumor Formation via Inhibiting the SERCA Calcium ATPase


G protein-coupled receptors (GPCRs) constitute the largest family of proteins that transmit signal across plasma membrane. Herpesviral GPCRs (vGPCRs) activate diverse signaling cascades and are implicated in viral pathogenesis (e.g., tumor development). In contrast to cellular GPCRs that are chiefly regulated via cognate ligand-association, vGPCRs are constitutively active independent of ligand-binding. vGPCRs provide useful tools to dissect signal transduction from plasma membrane receptors to nuclear transcription factors. To probe the activation of nuclear factor of T cells (NFAT), we demonstrate that vGPCRs target the ER calcium ATPase to increase cytosolic calcium concentration and activate NFAT. Inhibition of NFAT activation impairs tumor formation induced by vGPCRs, implying the antitumor therapeutic potential via disabling NFAT activation.


Vyšlo v časopise: Herpesviral G Protein-Coupled Receptors Activate NFAT to Induce Tumor Formation via Inhibiting the SERCA Calcium ATPase. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004768
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004768

Souhrn

G protein-coupled receptors (GPCRs) constitute the largest family of proteins that transmit signal across plasma membrane. Herpesviral GPCRs (vGPCRs) activate diverse signaling cascades and are implicated in viral pathogenesis (e.g., tumor development). In contrast to cellular GPCRs that are chiefly regulated via cognate ligand-association, vGPCRs are constitutively active independent of ligand-binding. vGPCRs provide useful tools to dissect signal transduction from plasma membrane receptors to nuclear transcription factors. To probe the activation of nuclear factor of T cells (NFAT), we demonstrate that vGPCRs target the ER calcium ATPase to increase cytosolic calcium concentration and activate NFAT. Inhibition of NFAT activation impairs tumor formation induced by vGPCRs, implying the antitumor therapeutic potential via disabling NFAT activation.


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