Rare Diseases Symptoms Automatic Extraction

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-κB (NF-κB)-dependent cellular survival in both PEL cells and primary B cells from HIV-negative KS patients. We further identified within vGPCR an AP2 consensus binding motif, Y326GLF, that directs its localization between the plasma membrane and clathrin-coated vesicles. The introduction of a mutation in this site (Y326A) 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 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