YGLF motif in the Kaposi sarcoma herpes virus G-protein-coupled receptor adjusts NF-κB activation and paracrine actions.

[primary effusion lymphoma]

Kaposi sarcoma (KS ) and primary effusion lymphoma (PEL ) are two pathologies associated with KS herpes virus (KSHV /HHV-8 ) infection . KSHV genome contains several oncogenes , among which , the viral G-protein-coupled receptor (vGPCR open reading frame 74 ) has emerged as a major factor in KS pathogenicity . Indeed , vGPCR is a constitutively active receptor , whose expression is sufficient to drive cell transformation in vitro and tumour development in mice . However , neither the role of vGPCR in KSHV-infected B-lymphocytes nor the molecular basis for its constitutive activation is well understood . Here , we show that vGPCR expression contributes to nuclear factor -κ B (NF-κB )-dependent cellular survival in both PEL cells and primary B cells from HIV-negative KS patients . We further identified within vGPCR an AP 2 consensus binding motif , Y 326 GLF , that directs its localization between the plasma membrane and clathrin-coated vesicles . The introduction of a mutation in this site (Y 326 A ) increased NF-κB activity and proinflammatory cytokines production . This correlated with exacerbated morphological rearrangement , migration and proliferation of non-infected monocytes . Collectively , our work raises the possibility that KSHV-infected B-lymphocytes use vGPCR to impact ultimately the immune response and communication within the tumour microenvironment in KSHV-associated pathologies .Oncogene advance online publication , 2 December 2013 ; doi :10 .1038 /onc .2013 .503 .

Diseases
Validation

Diseases presenting "sarcoma" symptom

alpha-thalassemia

carcinoma of the gallbladder

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

erdheim-chester disease

esophageal adenocarcinoma

focal myositis

hodgkin lymphoma, classical

liposarcoma

lymphangioleiomyomatosis

malignant atrophic papulosis

pleomorphic liposarcoma

primary effusion lymphoma

severe combined immunodeficiency

waldenström macroglobulinemia

well-differentiated liposarcoma

This symptom has already been validated