vGPCR, The Great Escape
Abstract
Kaposi Sarcoma (KS), a connective tissue cancer that may affect the skin and internal organs, is associated with human herpes virus 8 (HHV-8) infection. Among the oncogenes encoded by HHV8, the viral G protein coupled receptor (vGPCR ORF74) was found instrumental for sarcomagenesis initiation and progression. Indeed, vGPCR displays permanent activation, and is sufficient to induce tumor development in mice. However, the molecular mechanisms controlling vGPCR expression and activation remain poorly understood. Here, we present recent data from our group highlighting the presence of an endocytosis motif (Y326GLF) in the vGPCR C-terminal domain that orchestrates the receptor cellular localization, as well as its signaling and paracrine actions. We further show that this YGLF motif controls TLR4 surface expression, and may thus assure immune surveillance. In conclusion, this work shed light on the importance of vGPCR cellular localization and trafficking for its pathogenicity.
